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Table of Content

    15 May 2026, Volume 21 Issue 5 Previous Issue   
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    大型哺乳动物大脑结构的可塑性:不仅仅是缩小道路
    Marco Ghibaudi, Alessandro Zanone, Luca Bonfanti
    2026, 21 (5):  1669-1680.  doi: 10.4103/NRR.NRR-D-24-01438
    Abstract ( 87 )   PDF (6907KB) ( 12 )   Save
    The capacity of the central nervous system for structural plasticity and regeneration is commonly believed to show a decreasing progression from “small and simple” brains to the larger, more complex brains of mammals. However, recent findings revealed that some forms of neural plasticity can show a reverse trend. Although plasticity is a well-preserved, transversal feature across the animal world, a variety of cell populations and mechanisms seem to have evolved to enable structural modifications to take place in widely different brains, likely as adaptations to selective pressures. Increasing evidence now indicates that a trade-off has occurred between regenerative (mostly stem cell–driven) plasticity and developmental (mostly juvenile) remodeling, with the latter primarily aimed not at brain repair but rather at “sculpting” the neural circuits based on experience. In particular, an evolutionary trade-off has occurred between neurogenic processes intended to support the possibility of recruiting new neurons throughout life and the different ways of obtaining new neurons, and between the different brain locations in which plasticity occurs. This review first briefly surveys the different types of plasticity and the complexity of their possible outcomes and then focuses on recent findings showing that the mammalian brain has a stem cell–independent integration of new neurons into pre-existing (mature) neural circuits. This process is still largely unknown but involves neuronal cells that have been blocked in arrested maturation since their embryonic origin (also termed “immature” or “dormant” neurons). These cells can then restart maturation throughout the animal’s lifespan to become functional neurons in brain regions, such as the cerebral cortex and amygdala, that are relevant to high-order cognition and emotions. Unlike stem cell–driven postnatal/adult neurogenesis, which significantly decreases from small-brained, short-living species to large-brained ones, immature neurons are particularly abundant in large-brained, long-living mammals, including humans. The immature neural cell populations hosted in these complex brains are an interesting example of an “enlarged road” in the phylogenetic trend of plastic potential decreases commonly observed in the animal world. The topic of dormant neurons that covary with brain size and gyrencephaly represents a prospective turning point in the field of neuroplasticity, with important translational outcomes. These cells can represent a reservoir of undifferentiated neurons, potentially granting plasticity within the high-order circuits subserving the most sophisticated cognitive skills that are important in the growing brains of young, healthy individuals and are frequently affected by debilitating neurodevelopmental and degenerative disorders.
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    Lactate and lactylation modifications in neurological disorders
    Yu Gu, Keyang Chen, Chunyan Lei , Xinglong Yang, Lu Wang, Linhu Zhao, Wen Jiang, Qionghua Deng
    2026, 21 (5):  1681-1697.  doi: 10.4103/NRR.NRR-D-24-01344
    Abstract ( 233 )   PDF (3568KB) ( 283 )   Save

    Research into lactylation modifications across various target organs in both health and disease has gained significant attention. Many essential life processes and the onset of diseases are not only related to protein abundance but are also primarily regulated by various post-translational protein modifications. Lactate, once considered merely a byproduct of anaerobic metabolism, has emerged as a crucial energy substrate and signaling molecule involved in both physiological and pathological processes within the nervous system. Furthermore, recent studies have emphasized the significant role of lactate in numerous neurological diseases, including Alzheimer’s disease, Parkinson’s disease, acute cerebral ischemic stroke, multiple sclerosis, Huntington’s disease, and myasthenia gravis. The purpose of this review is to synthesize the current research on lactate and lactylation modifications in neurological diseases, aiming to clarify their mechanisms of action and identify potential therapeutic targets. As such, this work provides an overview of the metabolic regulatory roles of lactate in various disorders, emphasizing its involvement in the regulation of brain function. Additionally, the specific mechanisms of brain lactate metabolism are discussed, suggesting the unique roles of lactate in modulating brain function. As a critical aspect of lactate function, lactylation modifications, including both histone and non-histone lactylation, are explored, with an emphasis on recent advancements in identifying the key regulatory enzymes of such modifications, such as lactylation writers and erasers. The effects and specific mechanisms of abnormal lactate metabolism in diverse neurological diseases are summarized, revealing that lactate acts as a signaling molecule in the regulation of brain functions and that abnormal lactate metabolism is implicated in the progression of various neurological disorders. Future research should focus on further elucidating the molecular mechanisms underlying lactate and lactylation modifications and exploring their potential as therapeutic targets for neurological diseases.

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    Synaptic pruning mechanisms and application of emerging imaging techniques in neurological disorders
    Yakang Xing, Yi Mo, Qihui Chen, Xiao Li
    2026, 21 (5):  1698-1714.  doi: 10.4103/NRR.NRR-D-24-01127
    Abstract ( 135 )   PDF (17841KB) ( 19 )   Save
    Synaptic pruning is a crucial process in synaptic refinement, eliminating unstable synaptic connections in neural circuits. This process is triggered and regulated primarily by spontaneous neural activity and experience-dependent mechanisms. The pruning process involves multiple molecular signals and a series of regulatory activities governing the “eat me” and “don’t eat me” states. Under physiological conditions, the interaction between glial cells and neurons results in the clearance of unnecessary synapses, maintaining normal neural circuit functionality via synaptic pruning. Alterations in genetic and environmental factors can lead to imbalanced synaptic pruning, thus promoting the occurrence and development of autism spectrum disorder, schizophrenia, Alzheimer’s disease, and other neurological disorders. In this review, we investigated the molecular mechanisms responsible for synaptic pruning during neural development. We focus on how synaptic pruning can regulate neural circuits and its association with neurological disorders. Furthermore, we discuss the application of emerging optical and imaging technologies to observe synaptic structure and function, as well as their potential for clinical translation. Our aim was to enhance our understanding of synaptic pruning during neural development, including the molecular basis underlying the regulation of synaptic function and the dynamic changes in synaptic density, and to investigate the potential role of these mechanisms in the pathophysiology of neurological diseases, thus providing a theoretical foundation for the treatment of neurological disorders.
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    Neuroinflammation strokes the brain: A double-edged sword in ischemic stroke
    Giorgia Lombardozzi , Vanessa Castelli , Chiara Giorgi, Annamaria Cimini, Michele d’Angelo
    2026, 21 (5):  1715-1722.  doi: 10.4103/NRR.NRR-D-24-01456
    Abstract ( 71 )   PDF (1325KB) ( 32 )   Save
    Stroke is a major cause of death and disability worldwide. It is characterized by a highly interconnected and multiphasic neuropathological cascade of events, in which an intense and protracted inflammatory response plays a crucial role in worsening brain injury. Neuroinflammation, a key player in the pathophysiology of stroke, has a dual role. In the acute phase of stroke, neuroinflammation exacerbates brain injury, contributing to neuronal damage and blood–brain barrier disruption. This aspect of neuroinflammation is associated with poor neurological outcomes. Conversely, in the recovery phase following stroke, neuroinflammation facilitates brain repair processes, including neurogenesis, angiogenesis, and synaptic plasticity. The transition of neuroinflammation from a harmful to a reparative role is not well understood. Therefore, this review seeks to explore the mechanisms underlying this transition, with the goal of informing the development of therapeutic interventions that are both time- and context-specific. This review aims to elucidate the complex and dual role of neuroinflammation in stroke, highlighting the main actors, biomarkers of the disease, and potential therapeutic approaches.
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    The critical role of iron homeostasis in neurodegenerative diseases
    Tiantian Liang, Jiasen Xu, Yan Zhu, He Zhao, Xiaoyu Zhai, Qi Wang, Xiaohui Ma, Limei Cui, Yan Sun
    2026, 21 (5):  1723-1737.  doi: 10.4103/NRR.NRR-D-24-01382
    Abstract ( 109 )   PDF (2712KB) ( 170 )   Save
    Neurodegenerative diseases are prevalent conditions that greatly impact human health. These diseases are primarily characterized by the progressive loss and eventual death of neuronal function, although the precise mechanisms underlying these processes remain incompletely understood. Iron is an essential trace element in the human body, playing a crucial role in various biological processes. The maintenance of iron homeostasis relies on the body’s intricate and nuanced regulatory mechanisms. In recent years, considerable attention has been directed toward the relationship between dysregulated iron homeostasis and neurodegenerative diseases. The regulation of iron homeostasis within cells is crucial for maintaining proper nervous system function. Research has already revealed that disruptions in iron homeostasis may lead to ferroptosis and oxidative stress, which, in turn, can impact neuronal health and contribute to the development of neurodegenerative diseases. This article primarily explores the intimate relationship between iron homeostasis and neurodegenerative diseases, aiming to provide novel insights and strategies for treating these debilitating conditions.
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    Drug-delivery strategies using biomaterials in the field of nerve regeneration
    Linbin Xu, Chao Zhou, Xu Wang, Cunyi Fan
    2026, 21 (5):  1738-1763.  doi: 10.4103/NRR.NRR-D-25-00027
    Abstract ( 133 )   PDF (4474KB) ( 54 )   Save
    Neural injuries can cause considerable functional impairments, and both central and peripheral nervous systems have limited regenerative capacity. The existing conventional pharmacological treatments in clinical practice show poor targeting, rapid drug clearance from the circulatory system, and low therapeutic efficiency. Therefore, in this review, we have first described the mechanisms underlying nerve regeneration, characterized the biomaterials used for drug delivery to facilitate nerve regeneration, and highlighted the functionalization strategies used for such drug-delivery systems. These systems mainly use natural and synthetic polymers, inorganic materials, and hybrid systems with advanced drug-delivery abilities, including nanoparticles, hydrogels, and scaffoldbased systems. Then, we focused on comparing the types of drug-delivery systems for neural regeneration as well as the mechanisms and challenges associated with targeted delivery of drugs to facilitate neural regeneration. Finally, we have summarized the clinical application research and limitations of targeted delivery of these drugs. These biomaterials and drug-delivery systems can provide mechanical support, sustained release of bioactive molecules, and enhanced intercellular contact, ultimately reducing cell apoptosis and enhancing functional recovery. Nevertheless, immune reactions, degradation regulation, and clinical translations remain major unresolved challenges. Future studies should focus on optimizing biomaterial properties, refining delivery precision, and overcoming translational barriers to advance these technologies toward clinical applications.
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    Emerging nanoparticle-based strategies to provide therapeutic benefits for stroke
    Javaria Sundus, Nashwa Amin, Irum Naz Abbasi, Fei Wu, Azhar B. Hussien, Benson OA Botchway, Suhong Ye, Qining Yang, Marong Fang
    2026, 21 (5):  1764-1782.  doi: 10.4103/NRR.NRR-D-24-01492
    Abstract ( 84 )   PDF (9625KB) ( 16 )   Save
    Functional neurological recovery remains the primary objective when treating ischemic stroke. However, current therapeutic approaches often fall short of achieving optimal outcomes. One of the most significant challenges in stroke treatment is the effective delivery of neuroprotective agents across the blood–brain barrier to ischemic regions within the brain. The blood–brain barrier, while essential for protecting the brain from harmful substances, also restricts the passage of many therapeutic compounds, thus limiting their efficacy. In this review, we summarizes the emerging role of nanoparticle-based therapies for the treatment of ischemic stroke and investigate their potential to revolutionize drug delivery, enhance neuroprotection, and promote functional recovery. Recent advancements in nanotechnology have led to the development of engineered nanoparticles specifically designed to overcome the blood–brain barrier, thus enabling the targeted delivery of therapeutic agents directly to the affected brain areas. Preclinical studies have demonstrated the remarkable potential of nanoparticle-based therapies to activate key neuroprotective pathways, such as the phosphoinositide 3-kinase/protein kinase B/cAMP response element-binding protein signaling cascade, which is crucial for neuronal survival, synaptic plasticity, and post-stroke recovery. By modulating these pathways, nanoparticles could mitigate neuronal damage, reduce inflammation, and promote tissue repair. Furthermore, nanoparticles offer a unique advantage by enabling multimodal therapeutic strategies that simultaneously target multiple pathological mechanisms of ischemic stroke, including oxidative stress, neuroinflammation, and apoptosis. This multifaceted approach enhances the overall efficacy of treatment, addressing the complex and interconnected processes that contribute to stroke-related brain injury. Surface modifications, such as functionalization with specific ligands or targeting molecules, further improve the precision of drug delivery, enhance targeting specificity, and prolong systemic circulation, thereby optimizing therapeutic outcomes. Nanoparticlebased therapeutics represent a paradigm shift for the management of stroke and provide a promising avenue for reducing post-stroke disability and improving the outcomes of long-term rehabilitation. By combining targeted drug delivery with the ability to modulate critical neuroprotective pathways, nanoparticles hold the potential to transform the treatment landscape for ischemic stroke. However, while preclinical data are highly encouraging, significant challenges remain in translating these advancements into clinical practice. Further research is needed to refine nanoparticle designs, optimize their safety profiles, and ensure their scalability for widespread application. Rigorous clinical trials are essential to validate their efficacy, assess long-term biocompatibility, and address potential off-target effects. The integration of interdisciplinary approaches, combining insights from nanotechnology, neuroscience, and pharmacology, will be critical if we are to overcome these challenges. Ultimately, nanoparticle-based therapies offer a foundation for innovative, precisionbased treatments that could significantly improve outcomes for stroke patients, thus paving the way for a new era in stroke care and neurological rehabilitation.
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    Effects of quercetin and its derivatives in in vivo models of neuroinflammation: A systematic review and meta-analysis
    Michele Goulart dos Santos , Bruno Dutra Arbo , Mariana Appel Hort
    2026, 21 (5):  1783-1792.  doi: 10.4103/NRR.NRR-D-24-01175
    Abstract ( 92 )   PDF (2887KB) ( 16 )   Save
    Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions. The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammatory drugs, which have a range of serious adverse effects. As an alternative, naturally derived molecules such as quercetin and its derivatives show promising anti-inflammatory properties and beneficial effects on various physiological functions. Our objective was to synthesize the evidence on the anti-inflammatory effect of quercetin and its derivatives in in vivo models, in the face of neuroinflammatory insults induced by lipopolysaccharide, through a systematic review and meta-analysis. A search of the preclinical literature was conducted across four databases (PubMed, Web of Science, Scielo, and Google Scholar). Studies were selected based on inclusion and exclusion criteria, assessed for methodological quality using CAMARADES, and risk of bias using the SYRCLE tool, and data were extracted from the studies. The quantitative assessment of quercetin effects on the expression of pro-inflammatory cytokines and microgliosis was performed through a meta-analysis. A total of 384 potentially relevant articles were identified, of which 11 studies were included in the analysis. The methodological quality was assessed, resulting in an average score of 5.8/10, and the overall risk of bias analysis revealed a lack of methodological clarity in most studies. Furthermore, through the meta-analysis, it was observed that treatment with quercetin statistically reduces pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin 6, interleukin 1β (n = 89; SMD = –2.00; 95% CI: –3.29 to –0.71), and microgliosis (n = 33; SMD = –2.56; 95% CI: –4.07 to –1.10). In terms of underlying mechanisms, quercetin and its derivatives exhibit antioxidant and anti-apoptotic properties, possibly through the nuclear factor erythroid 2-related factor 2 (Nrf2)/ HO-1 pathways, increasing the expression of antioxidant enzymes and reducing reactive species, and modulating the caspase pathway, increasing levels of anti-apoptotic proteins and decreasing proapoptotic proteins. Quercetin and its derivatives exhibit highly pleiotropic actions that simultaneously contribute to preventing neuroinflammation. However, despite promising results in animal models, future directions should focus on well-designed clinical studies to assess the safety, bioavailability, and efficacy of quercetin and its derivatives in humans. Additionally, standardization of methods and dosages in studies is crucial to ensure consistency of findings and optimize their application in clinical settings.
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    Drug delivery strategies for neuroprotective therapy in ischemic stroke: Application of nanotechnology
    Zhan Jiang, Qi Chen, Huanghao Yang
    2026, 21 (5):  1793-1808.  doi: 10.4103/NRR.NRR-D-24-01383
    Abstract ( 107 )   PDF (37042KB) ( 10 )   Save
    The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity, oxidative stress, inflammatory responses, and blood–brain barrier disruption. While vascular recanalization treatments such as thrombolysis and mechanical thrombectomy have achieved some success, reperfusion injury remains a significant contributor to the exacerbation of brain injury. This emphasizes the need for developing neuroprotective strategies to mitigate this type of injury. The purpose of this review was to examine the application of nanotechnology in the treatment of ischemic stroke, covering research progress in nanoparticlebased drug delivery, targeted therapy, and antioxidant and anti-inflammatory applications. Nanobased drug delivery systems offer several advantages compared to traditional therapies, including enhanced blood–brain barrier penetration, prolonged drug circulation time, improved drug stability, and targeted delivery. For example, inorganic nanoparticles, such as those based on CeO2, have been widely studied for their strong antioxidant capabilities. Biomimetic nanoparticles, such as those coated with cell membranes, have garnered significant attention owing to their excellent biocompatibility and targeting abilities. Nanoparticles can be used to deliver a wide range of neuroprotective agents, such as antioxidants (e.g., edaravone), anti-inflammatory drugs (e.g., curcumin), and neurotrophic factors. Nanotechnology significantly enhances the efficacy of these drugs while minimizing adverse reactions. Although nanotechnology has demonstrated great potential in animal studies, its clinical application still faces several challenges, including the long-term safety of nanoparticles, the feasibility of large-scale production, quality control, and the ability to predict therapeutic effects in humans. In summary, nanotechnology holds significant promise for the treatment of ischemic stroke. Future research should focus on further exploring the mechanisms of action of nanoparticles, developing multifunctional nanoparticles, and validating their safety and efficacy through rigorous clinical trials. Moreover, interdisciplinary collaboration is essential for advancing the use of nanotechnology in stroke treatment.
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    Interleukin-17 family in health and immune diseases: From origin to clinical implications
    Guozhen Deng, Mengdi Guo, Jiahui Fan, Weiyan Wang, Mei-Ling Jiang, Cun-Jin Zhang
    2026, 21 (5):  1809-1833.  doi: 10.4103/NRR.NRR-D-25-00026
    Abstract ( 110 )   PDF (6219KB) ( 38 )   Save
    The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions, including regulating the inflammatory cascade in various autoimmune and inflammatory diseases, such as multiple sclerosis, neuromyelitis optica spectrum disorder, myasthenia gravis, Guillain–Barre syndrome, acute disseminated encephalomyelitis, diabetes, inflammatory skin diseases, joint inflammation, and cancer. Although the function of the interleukin-17 family has attracted increasing research attention over many years, the expression, function, and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood. Currently, the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases, with several monoclonal antibodies against interleukin17A having been successfully used in clinical practice. Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated. This review first summarizes the recent advancements in understanding the physicochemical properties, physiological functions, cellular origins, and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family. Subsequently, the function of interleukin-17 in various immune diseases is discussed, and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives. Then, the current status of targeted interleukin-17 therapy is summarized, and the effectiveness and safety of targeted interleukin-17 therapy are analyzed. Finally, the clinical application prospects of targeting the interleukin-17 pathway are discussed.
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    Novel therapies for myasthenia gravis: Translational research from animal models to clinical application
    Benedetta Sorrenti, Christian Laurini, Luca Bosco, Camilla Mirella Maria Strano, Adele Ratti, Yuri Matteo Falzone, Stefano Carlo Previtali
    2026, 21 (5):  1834-1848.  doi: 10.4103/NRR.NRR-D-24-01011
    Abstract ( 94 )   PDF (3929KB) ( 131 )   Save
    Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in their serum, targeting acetylcholine receptor, muscle-specific kinase, or related proteins. Current treatment for myasthenia gravis involves symptomatic therapy, immunosuppressive drugs such as corticosteroids, azathioprine, and mycophenolate mofetil, and thymectomy, which is primarily indicated in patients with thymoma or thymic hyperplasia. However, this condition continues to pose significant challenges including an unpredictable and variable disease progression, differing response to individual therapies, and substantial longterm side effects associated with standard treatments (including an increased risk of infections, osteoporosis, and diabetes), underscoring the necessity for a more personalized approach to treatment. Furthermore, about fifteen percent of patients, called “refractory myasthenia gravis patients”, do not respond adequately to standard therapies. In this context, the introduction of molecular therapies has marked a significant advance in myasthenia gravis management. Advances in understanding myasthenia gravis pathogenesis, especially the role of pathogenic antibodies, have driven the development of these biological drugs, which offer more selective, rapid, and safer alternatives to traditional immunosuppressants. This review aims to provide a comprehensive overview of emerging therapeutic strategies targeting specific immune pathways in myasthenia gravis, with a particular focus on preclinical evidence, therapeutic rationale, and clinical translation of B-cell depletion therapies, neonatal Fc receptor inhibitors, and complement inhibitors.
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    Latest progress and challenges in drug development for degenerative motor neuron diseases
    Xiangjin Wen, Tianxiang Lan, Weiming Su , Bei Cao , Yi Wang, Yongping Chen
    2026, 21 (5):  1849-1863.  doi: 10.4103/NRR.NRR-D-24-01266
    Abstract ( 123 )   PDF (2605KB) ( 92 )   Save
    Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions. They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute course contingent upon the site of damage. The main types include amyotrophic lateral sclerosis, progressive muscular atrophy, primary lateral sclerosis, and progressive bulbar palsy, the pathological processes of which are largely identical, with the main disparity lying in the location of the lesions. Amyotrophic lateral sclerosis is the representative condition in this group of diseases, while other types are its variants. Hence, this article mainly focuses on the advancements and challenges in drug research for amyotrophic lateral sclerosis but also briefly addresses several other important degenerative motor neuron diseases. Although the precise pathogenesis remains elusive, recent advancements have shed light on various theories, including gene mutation, excitatory amino acid toxicity, autoimmunology, and neurotrophic factors. The US Food and Drug Administration has approved four drugs for use in delaying the progression of amyotrophic lateral sclerosis: riluzole, edaravone, AMX0035, and tofersen, with the latter being the most recent to receive approval. However, following several phase III trials that failed to yield favorable outcomes, AMX0035 has been voluntarily withdrawn from both the US and Canadian markets. This article presents a comprehensive summary of drug trials primarily completed between January 1, 2023, and June 30, 2024, based on data sourced from clinicaltrials.gov. Among these trials, five are currently in phase I, seventeen are in phase II, and eleven are undergoing phase III evaluation. Notably, 24 clinical trials are now investigating potential disease-modifying therapy drugs, accounting for the majority of the drugs included in this review. Some promising drugs being investigated in preclinical studies, such as ATH-1105, are included in our analysis, and another review in frontiers in gene therapy and immunotherapy has demonstrated their therapeutic potential for motor neuron diseases. This article was written to be an overview of research trends and treatment prospects related to motor neuron disease drugs, with the aim of highlighting the latest potentialities for clinical therapy.
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    Neuroinflammation in neurodegenerative diseases: Focusing on the mediation of T lymphocytes
    Ke Li, Rongsha Chen, Ruohua Wang, Wenhui Fan, Ninghui Zhao, Zhongshan Yang, Jinyuan Yan
    2026, 21 (5):  1864-1889.  doi: 10.4103/NRR.NRR-D-24-01539
    Abstract ( 89 )   PDF (28147KB) ( 9 )   Save
    Neurodegenerative diseases are a group of illnesses characterized by the gradual deterioration of the central nervous system, leading to a decline in patients’ cognitive, motor, and emotional abilities. Neuroinflammation plays a significant role in the progression of these diseases. However, there is limited research on therapeutic approaches to specifically target neuroinflammation. The role of T lymphocytes, which are crucial mediators of the adaptive immune response, in neurodegenerative diseases has been increasingly recognized. This review focuses on the involvement of T lymphocytes in the neuroinflammation associated with neurodegenerative diseases. The pathogenesis of neurodegenerative diseases is complex, involving multiple mechanisms and pathways that contribute to the gradual degeneration of neurons, and T cells are a key component of these processes. One of the primary factors driving neuroinflammation in neurodegenerative diseases is the infiltration of T cells and other neuroimmune cells, including microglia, astrocytes, B cells, and natural killer cells. Different subsets of CD4+ T cells, such as Th1, Th2, Th17, and regulatory T cells, can differentiate into various cell types and perform distinct roles within the neuroinflammatory environment of neurodegenerative diseases. Additionally, CD8+ T cells, which can directly regulate immune responses and kill target cells, also play several important roles in neurodegenerative diseases. Clinical trials investigating targeted T cell therapies for neurodegenerative diseases have shown that, while some patients respond positively, others may not respond as well and may even experience adverse effects. Targeting T cells precisely is challenging due to the complexity of immune responses in the central nervous system, which can lead to undesirable side effects. However, with new insights into the pathophysiology of neurodegenerative diseases, there is hope for the establishment of a solid theoretical foundation upon which innovative treatment strategies that target T cells can be developed in the future.
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    Extracellular nucleotides mediate viral central nervous system infections: Key alarmins of neuroinflammation and neurodegeneration
    Raíssa Leite-Aguiar, Elaine Paiva-Pereira, Robson Coutinho-Silva , Cláudia Pinto Figueiredo, Luiz Eduardo Baggio Savio
    2026, 21 (5):  1890-1898.  doi: 10.4103/NRR.NRR-D-24-01464
    Abstract ( 99 )   PDF (3491KB) ( 35 )   Save
    Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration. Viral pathogens or their products can invade the central nervous system and cause damage, leading to meningitis, encephalitis, meningoencephalitis, myelitis, or post-infectious demyelinating diseases. Although neuroinflammation initially has a protective function, chronic inflammation can contribute to the development of neurodegenerative diseases. Mechanisms such as protein aggregation and cellular disturbances are implicated with specific viruses such as herpes simplex virus type 1 and Epstein-Barr virus being associated with Alzheimer’s disease and multiple sclerosis, respectively. Extracellular nucleotides, particularly adenosine triphosphate and its metabolites are released from activated, infected, and dying cells, acting as alarmins mediating neuroinflammation and neurodegeneration. When viruses infect central nervous system cells, adenosine triphosphate is released as an alarmin, triggering inflammatory responses. This process is mediated by purinergic receptors, divided into two families: P1, which responds to adenosine, and P2, activated by adenosine triphosphate and other nucleotides. This review highlights how specific viruses, such as human immunodeficiency virus type 1, Theiler’s murine encephalomyelitis virus, herpes simplex virus type 1, Epstein-Barr virus, dengue virus, Zika virus, and severe acute respiratory syndrome coronavirus 2, can initiate inflammatory responses through the release of extracellular nucleotides, particularly adenosine triphosphate, which act as critical mediators in the progression of neuroinflammation and neurodegenerative disorders. A better understanding of purinergic signaling pathways in these diseases may suggest new potential therapeutic strategies for targeting neuroinflammation to mitigate the long-term consequences of viral infections in the central nervous system.
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    Deep brain stimulation for the treatment of Alzheimer’s disease: A safer and more effective strategy
    Fan Zhang, Yao Meng, Wei Zhang
    2026, 21 (5):  1899-1909.  doi: 10.4103/NRR.NRR-D-24-01088
    Abstract ( 99 )   PDF (1911KB) ( 93 )   Save
    Alzheimer’s disease is the most common type of cognitive disorder, and there is an urgent need to develop more effective, targeted and safer therapies for patients with this condition. Deep brain stimulation is an invasive surgical treatment that modulates abnormal neural activity by implanting electrodes into specific brain areas followed by electrical stimulation. As an emerging therapeutic approach, deep brain stimulation shows significant promise as a potential new therapy for Alzheimer’s disease. Here, we review the potential mechanisms and therapeutic effects of deep brain stimulation in the treatment of Alzheimer’s disease based on existing clinical and basic research. In clinical studies, the most commonly targeted sites include the fornix, the nucleus basalis of Meynert, and the ventral capsule/ventral striatum. Basic research has found that the most frequently targeted areas include the fornix, nucleus basalis of Meynert, hippocampus, entorhinal cortex, and rostral intralaminar thalamic nucleus. All of these individual targets exhibit therapeutic potential for patients with Alzheimer’s disease and associated mechanisms of action have been investigated. Deep brain stimulation may exert therapeutic effects on Alzheimer’s disease through various mechanisms, including reducing the deposition of amyloid-β, activation of the cholinergic system, increasing the levels of neurotrophic factors, enhancing synaptic activity and plasticity, promoting neurogenesis, and improving glucose metabolism. Currently, clinical trials investigating deep brain stimulation for Alzheimer’s disease remain insufficient. In the future, it is essential to focus on translating preclinical mechanisms into clinical trials. Furthermore, consecutive follow-up studies are needed to evaluate the long-term safety and efficacy of deep brain stimulation for Alzheimer’s disease, including cognitive function, neuropsychiatric symptoms, quality of life and changes in Alzheimer’s disease biomarkers. Researchers must also prioritize the initiation of multi-center clinical trials of deep brain stimulation with large sample sizes and target earlier therapeutic windows, such as the prodromal and even the preclinical stages of Alzheimer’s disease. Adopting these approaches will permit the efficient exploration of more effective and safer deep brain stimulation therapies for patients with Alzheimer’s disease.
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    Photoacoustic technologies in nervous system disorders: An emerging strategy for neuromodulation
    Chenyuan Ding, Penghao Liu, Zhuofan Xu, Yuanchen Cheng, Han Yu, Lei Cheng, Zan Chen, Fengzeng Jian, Wanru Duan
    2026, 21 (5):  1910-1925.  doi: 10.4103/NRR.NRR-D-24-01191
    Abstract ( 114 )   PDF (1976KB) ( 59 )   Save
    Spinal cord injury is a severe neurological disorder; however, current treatment methods often fail to restore nerve function effectively. Spinal cord stimulation via electrical signals is a promising therapeutic modality for spinal cord injury. Based on similar principles, this review aims to explore the potential of optical and acoustic neuromodulation techniques, emphasizing their benefits in the context of spinal cord injury. Photoacoustic imaging, renowned for its noninvasive nature, high-resolution capabilities, and cost-effectiveness, is well recognized for its role in early diagnosis, dynamic monitoring, and surgical guidance in stem cell therapies for spinal cord injury. Moreover, photoacoustodynamic therapy offers multiple pathways for tissue regeneration. Optogenetics and sonogenetics use genetic engineering to achieve precise neuronal activation, while photoacoustoelectric therapy leverages photovoltaic materials for electrical modulation of the nervous system, introducing an innovative paradigm for nerve system disorder management. Collectively, these advancements represent a transformative shift in the diagnosis and treatment of spinal cord injury, with the potential to significantly enhance nerve function remodeling and improve patient outcomes.
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    Mitochondrial dynamics dysfunction and neurodevelopmental disorders: From pathological mechanisms to clinical translation
    Ziqi Yang, Yiran Luo, Zaiqi Yang, Zheng Liu, Meihua Li, Xiao Wu, Like Chen, Wenqiang Xin
    2026, 21 (5):  1926-1946.  doi: 10.4103/NRR.NRR-D-24-01422
    Abstract ( 122 )   PDF (8468KB) ( 30 )   Save
    Mitochondrial dysfunction has emerged as a critical factor in the etiology of various neurodevelopmental disorders, including autism spectrum disorders, attention-deficit/hyperactivity disorder, and Rett syndrome. Although these conditions differ in clinical presentation, they share fundamental pathological features that may stem from abnormal mitochondrial dynamics and impaired autophagic clearance, which contribute to redox imbalance and oxidative stress in neurons. This review aimed to elucidate the relationship between mitochondrial dynamics dysfunction and neurodevelopmental disorders. Mitochondria are highly dynamic organelles that undergo continuous fusion and fission to meet the substantial energy demands of neural cells. Dysregulation of these processes, as observed in certain neurodevelopmental disorders, causes accumulation of damaged mitochondria, exacerbating oxidative damage and impairing neuronal function. The phosphatase and tensin homolog-induced putative kinase 1/E3 ubiquitin-protein ligase pathway is crucial for mitophagy, the process of selectively removing malfunctioning mitochondria. Mutations in genes encoding mitochondrial fusion proteins have been identified in autism spectrum disorders, linking disruptions in the fusion-fission equilibrium to neurodevelopmental impairments. Additionally, animal models of Rett syndrome have shown pronounced defects in mitophagy, reinforcing the notion that mitochondrial quality control is indispensable for neuronal health. Clinical studies have highlighted the importance of mitochondrial disturbances in neurodevelopmental disorders. In autism spectrum disorders, elevated oxidative stress markers and mitochondrial DNA deletions indicate compromised mitochondrial function. Attention-deficit/hyperactivity disorder has also been associated with cognitive deficits linked to mitochondrial dysfunction and oxidative stress. Moreover, induced pluripotent stem cell models derived from patients with Rett syndrome have shown impaired mitochondrial dynamics and heightened vulnerability to oxidative injury, suggesting the role of defective mitochondrial homeostasis in these disorders. From a translational standpoint, multiple therapeutic approaches targeting mitochondrial pathways show promise. Interventions aimed at preserving normal fusion-fission cycles or enhancing mitophagy can reduce oxidative damage by limiting the accumulation of defective mitochondria. Pharmacological modulation of mitochondrial permeability and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, an essential regulator of mitochondrial biogenesis, may also ameliorate cellular energy deficits. Identifying early biomarkers of mitochondrial impairment is crucial for precision medicine, since it can help clinicians tailor interventions to individual patient profiles and improve prognoses. Furthermore, integrating mitochondria-focused strategies with established therapies, such as antioxidants or behavioral interventions, may enhance treatment efficacy and yield better clinical outcomes. Leveraging these pathways could open avenues for regenerative strategies, given the influence of mitochondria on neuronal repair and plasticity. In conclusion, this review indicates mitochondrial homeostasis as a unifying therapeutic axis within neurodevelopmental pathophysiology. Disruptions in mitochondrial dynamics and autophagic clearance converge on oxidative stress, and researchers should prioritize validating these interventions in clinical settings to advance precision medicine and enhance outcomes for individuals affected by neurodevelopmental disorders.
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    Systematic review of mitochondrial dysfunction and oxidative stress in aging: A focus on neuromuscular junctions
    Senlin Chai, Ning Zhang, Can Cui, Zhengyuan Bao, Qianjin Wang, Wujian Lin, Ronald Man Yeung Wong, Sheung Wai Law, Rebecca Schönmehl, Christoph Brochhausen, Wing Hoi Cheung
    2026, 21 (5):  1947-1960.  doi: 10.4103/NRR.NRR-D-24-01338
    Abstract ( 137 )   PDF (6978KB) ( 26 )   Save
    Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases. The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia. However, the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood. A defined systematic search of the PubMed, Web of Science and Embase databases (last accessed on October 30, 2024) was conducted with search terms including ‘mitochondria’, ‘aging’ and ‘NMJ’. Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging. Twentyseven studies were included in this systematic review. This systematic review provides a summary of morphological, functional and biological changes in neuromuscular junction, mitochondrial morphology, biosynthesis, respiratory chain function, and mitophagy during aging. We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging. Aging is characterized by significant reductions in mitochondrial fusion/fission cycles, biosynthesis, and mitochondrial quality control, which may lead to neuromuscular junction dysfunction, denervation and poor physical performance. Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities, ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function. Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways, including the mitochondrial respiratory chain, energy deficiency, oxidative stress, and inflammation. Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation, resulting in muscle atrophy and a decrease in strength during aging. Physical therapy, pharmacotherapy, and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function. Therefore, mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.
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    Cell-based therapies for traumatic optic neuropathy: Recent advances, challenges, and perspectives
    Yuanhui Wang, Moxin Chen, Zhimin Tang, Ping Gu
    2026, 21 (5):  1961-1980.  doi: 10.4103/NRR.NRR-D-24-01322
    Abstract ( 150 )   PDF (5893KB) ( 67 )   Save
    Traumatic optic neuropathy is a form of optic neuropathy resulting from trauma. Its pathophysiological mechanisms involve primary and secondary injury phases, leading to progressive retinal ganglion cell loss and axonal degeneration. Contributing factors such as physical trauma, oxidative stress, neuroinflammation, and glial scar formation exacerbate disease progression and retinal ganglion cell death. Multiple forms of cell death—including apoptosis, pyroptosis, necroptosis, and ferroptosis— are involved at different disease stages. Although current treatments, such as corticosteroid therapy and surgical interventions, have limited efficacy, cell-based therapies have emerged as a promising approach that simultaneously promotes neuroprotection and retinal ganglion cell regeneration. This review summarizes recent advances in cell-based therapies for traumatic optic neuropathy. In the context of cell replacement therapy, retinal ganglion cell-like cells derived from embryonic stem cells and induced pluripotent stem cells—via chemical induction or direct reprogramming—have demonstrated the ability to integrate into the host retina and survive for weeks to months, potentially improving visual function. Mesenchymal stem cells derived from various sources, including bone marrow, umbilical cord, placenta, and adipose tissue, have been shown to enhance retinal ganglion cell survival, stimulate axonal regeneration, and support partial functional recovery. Additionally, neural stem/progenitor cells derived from human embryonic stem cells offer neuroprotective effects and function as “neuronal relays,” facilitating reconnection between damaged regions of the optic nerve and the visual pathway. Beyond direct cell transplantation, cell-derived products, such as extracellular vesicles and cell-extracted solutions, have demonstrated promising neuroprotective effects in traumatic optic neuropathy. Despite significant progress, several challenges remain, including limited integration of transplanted cells, suboptimal functional vision recovery, the need for precise timing and delivery methods, and an incomplete understanding of the role of the retinal microenvironment and glial cell activation in neuroprotection and neuroregeneration. Furthermore, studies with longer observation periods and deeper mechanistic insights into the therapeutic effects of cell-based therapies remain scarce. Two Phase I clinical trials have confirmed the safety and potential benefits of cell-based therapy for traumatic optic neuropathy, with reported improvements in visual acuity. However, further studies are needed to validate these findings and establish significant therapeutic outcomes. In conclusion, cell-based therapies hold great promise for treating traumatic optic neuropathy, but critical obstacles must be overcome to achieve functional optic nerve regeneration. Emerging bioengineering strategies, such as scaffold-based transplantation, may improve cell survival and axonal guidance. Successful clinical translation will require rigorous preclinical validation, standardized protocols, and the integration of advanced imaging techniques to optimize therapeutic efficacy.
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    Amyloid degradation mechanisms and potential synergistic effects
    Maksim I. Sulatsky , Olesya V. Stepanenko , Olga V. Stepanenko, Anna I. Sulatskaya
    2026, 21 (5):  1981-1982.  doi: 10.4103/NRR.NRR-D-24-01534
    Abstract ( 65 )   PDF (1337KB) ( 16 )   Save
    Currently, our understanding of the pathogenesis of major neurodegenerative disorders, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, is largely shaped by the amyloid cascade hypothesis. Particularly, this hypothesis posits that in Alzheimer’s disease, the aggregation of amyloid-beta peptide initiates a series of pathological processes leading to neuronal dysfunction and death (Zhang et al., 2024). Additionally, other mechanistic hypotheses, including tau protein hyperphosphorylation, metal ion dysregulation, and chronic neuroinflammation, contribute to the multifactorial nature of neurodegeneration. Such factors further exacerbate the impact of amyloids accumulation. These protein aggregates represent extremely stable structures that disrupt cellular functioning and initiate cascade inflammatory and oxidative processes, accelerating neurodegeneration. These processes involve microglial activation, inflammatory cytokine release, and impaired synaptic transmission, all exacerbating neuronal damage. Current treatments for neurodegenerative diseases linked to the accumulation of insoluble protein plaques focus mainly on symptomatic relief and slowing disease progression. For example, Alzheimer’s disease treatments often involve cholinesterase inhibitors and NMDA receptor antagonists (Cummings et al., 2023; Zhang et al., 2024). However, these drugs do not address one of the primary causes of degenerative changes—the accumulation of amyloid plaques (Zhang et al., 2023). Efforts to develop drugs targeting the degradation of amyloid fibrils and their aggregates have yet to yield effective and safe treatments. Several new medications following this approach, currently in various stages of development and clinical trials, have demonstrated limited efficacy despite initial optimism. In some cases, these drugs have caused serious side effects, such as brain edema and microhemorrhages (Zhang et al., 2023, 2024; Lasheen et al., 2024; Torres et al., 2024). Thus, despite years of research, no effective treatment has yet been developed to achieve the complete and safe degradation of amyloid fibrils. Challenges in developing an effective therapy for amyloidoses may partly arise from an insufficient understanding of the molecular mechanisms underlying the disruption of pathological aggregates by proposed drugs and the properties of amyloid degradation products. Obtaining such information is crucial for predicting the potential adverse effects of this therapy. In this regard, we aim to analyze the currently known mechanisms of amyloid degradation and evaluate their potential synergistic effects.
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    Functional central nervous system regeneration: Challenges from axons to circuits
    Apolline Delaunay , Mickaël Le Boulc’h , Stephane Belin , Homaira Nawabi
    2026, 21 (5):  1983-1984.  doi: 10.4103/NRR.NRR-D-24-01633
    Abstract ( 86 )   PDF (688KB) ( 20 )   Save
    The mature central nervous system (CNS, composed of the brain, spinal cord, olfactory and optic nerves) is unable to regenerate spontaneously after an insult, both in the cases of neurodegenerative diseases (for example Alzheimer’s or Parkinson’s disease) or traumatic injuries (such as spinal cord lesions). In the last 20 years, the field has made significant progress in unlocking axon regrowth. The lesion’s environment has been well characterized, notably the contribution of the glial scar and myelin debris-associated molecules to axon regeneration inhibition. Surprisingly, the modulation of these factors only promotes limited axon regrowth (Varadarajan et al., 2022). Thus, the focus has progressively shifted from the environment of the injured axons to the neurons themselves. Several regenerative models have been developed targeting different steps of gene expression from epigenetics to translation processes. For example, regarding transcription regulation, it has been found that the modulation of transcription factors, such as suppressor of cytokine signaling 3, a negative regulator of Janus kinases/signal transducers and activators of transcription pathway, the Krüppel-like factors family or c-myc could promote axon regeneration (Varadarajan et al., 2022). Activating the mammalian target of rapamycin pathway, a major regulator of protein translation also promotes regeneration (Varadarajan et al., 2022). Moreover, combinatorial approaches such as activation of mammalian target of rapamycin, Janus kinases/ signal transducers and activators of transcription pathways along with c-myc overexpression lead axon regeneration up to several millimeters from the eye to the brain (Belin et al., 2015). Even if these results are very exciting, functional recovery remains a pending issue. Indeed, recent work highlights that regrowing axons is not the only aspect necessary for circuit formation and several unexpected roadblocks have been uncovered: (i) the majority of regenerating axons do not reach their proper targets, (ii) nor do they regularly form synapses when they do reach their targets, and (iii) myelination in a regenerative context is still poorly characterized. In this article, we will discuss these challenges.
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    Iron dyshomeostasis links obesity and neurological diseases
    Bandy Chen
    2026, 21 (5):  1985-1986.  doi: 10.4103/NRR.NRR-D-24-01657
    Abstract ( 76 )   PDF (2961KB) ( 9 )   Save
    With the industrialization of agriculture and the advancement of medical care, human life expectancy has increased considerably and continues to rise steadily. This results in novel and unprecedented challenges, namely obesity and neurodegeneration. Understanding the intimate link between these two pathologies will enhance our understanding of brain-body crosstalk to develop effective treatments to halt the rising rates of obesity and neurological disorders. Obesity increases the risk of cognitive decline and neurological disorders; however, it remains unclear the exact mechanisms of obesity-induced neurodegeneration. This perspective proposes iron as a nexus between obesity and neurological disorders through the reshaping of the neuro-glialvascular landscape.
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    Beyond the surface: Advancing neurorehabilitation with transcranial temporal interference stimulation — clinical applications and future prospects
    Camille E. Proulx, Friedhelm C. Hummel
    2026, 21 (5):  1987-1988.  doi: 10.4103/NRR.NRR-D-24-01573
    Abstract ( 98 )   PDF (1447KB) ( 126 )   Save
    Brain lesions, such as those caused by stroke or traumatic brain injury (TBI), frequently result in persistent motor and cognitive impairments that significantly affect the individual patient’s quality of life. Despite differences in the mechanisms of injury, both conditions share a high prevalence of motor and cognitive impairments. These deficits show only limited natural recovery. Therefore, the impairments following brain injury mandate better treatment and represent critically important targets for novel interventional strategies in neurorehabilitation. By focusing on improving recovery and promoting functional independence, neurorehabilitation plays a crucial role in helping individuals regain the ability to perform daily life activities, addressing the growing global burden of neurological disorders. Non-invasive brain stimulation has emerged as a promising approach to neurorehabilitation, with its capacity to modulate activity in targeted brain regions. Techniques such as transcranial direct current stimulation and transcranial magnetic stimulation (TMS) are among the most extensively studied, recognized for their potential to influence cortical activity and induce changes across motor, sensory, and cognitive networks. While these methods are considered safe compared to invasive alternatives, they have the limitation of only effectively targeting cortical brain regions. Considering the critical role, supported by imaging studies and animal models, of subcortical brain areas, such as the striatum, thalamus, or hippocampus for motor and cognitive processes, there is a growing need for non-invasive approaches capable of reaching deeper brain structures (Miyachi et al., 1997). Currently, a novel, promising, innovative, and safe neuromodulation technique called transcranial temporal interference stimulation (tTIS) has been introduced (Figure 1), with the potential to address these challenges by selectively targeting deeper brain regions without impacting overlying structures (Wessel et al., 2023; Beanato et al., 2024; Vassiliadis et al., 2024). As a novel approach, it is not surprising that research on its application in human neurorehabilitation remains limited. This manuscript seeks to provide an overview of tTIS in the context towards application in neurorehabilitation, particularly for stroke and TBI, to address current challenges, and, most importantly, to provide a forward-looking perspective on its future clinical applications and transformative impact on the field. Additionally, it highlights emerging areas of research and upcoming studies that promise to advance our understanding and implementation of this innovative technology.
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    Adipose tissue–brain crosstalk in comorbid obesity and traumatic brain injury: Insights into mechanisms
    Susan C. Burke, Bogdan A. Stoica, Rebecca J. Henry
    2026, 21 (5):  1989-1990.  doi: 10.4103/NRR.NRR-D-25-00023
    Abstract ( 86 )   PDF (1173KB) ( 42 )   Save
    Obese individuals who subsequently sustain a traumatic brain injury (TBI) exhibit worsened outcomes including longer periods of rehabilitation (Eagle et al., 2023). In obese individuals, prolonged symptomology is associated with increased levels of circulatory pro-inflammatory markers up to 1 year postTBI (Eagle et al., 2023). Despite this, the mechanisms driving worsened outcomes remain poorly understood. Expanding our understanding of the underlying mechanisms driving obesity-induced exacerbations of TBI deficits is important at a fundamental physiological level and for the identification of novel therapeutic approaches for TBI patients with underlying metabolic dysfunction.
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    Novel roles of DNA glycosylases in neurodegenerative diseases and aging
    Vinod Tiwari, Fivos Borbolis, Deborah L. Croteau, Konstantinos Palikaras , Vilhelm A. Bohr
    2026, 21 (5):  1991-1992.  doi: 10.4103/NRR.NRR-D-24-01588
    Abstract ( 87 )   PDF (1675KB) ( 37 )   Save
    Numerous neurological disorders negatively impact the nervous system, either through loss of neurons or by disrupting the normal functioning of neural networks. These impairments manifest as cognitive defects, memory loss, behavioral abnormalities, and motor dysfunctions. Decades of research have significantly advanced our understanding of the pathophysiology underlying neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease, amyotrophic lateral sclerosis, and others. Loss of dopaminergic neurons in the substantia nigra pars compacta with motor function defect is clinically associated with Parkinson’s disease, whereas the accumulation of amyloid-β plaques and tau neurofibrillary tangles is a main pathological hallmark of AD. Beyond these disease-specific mechanisms, key risk factors, such as aging, genomic stress, and mitochondrial dysfunction contribute broadly to the onset and progression of various neurological disorders (Tiwari and Wilson, 2019; Wilson et al., 2023). However, it is still unclear how these events promote the onset of pathological phenotypes and eventually lead to neuronal cell death. The DNA base excision repair (BER) pathway plays a vital role in the maintenance of genome stability and safeguarding human health by repairing endogenous and exogenous oxidative DNA damage. The BER pathway begins with a glycosylase enzyme that recognizes and removes the damaged base, creating an apurinic/ apyrimidinic site. In the next step, an apurinic/ apyrimidinic endonuclease cleaves the DNA backbone at the apurinic/apyrimidinic site, generating a single-strand break. This is followed by gap filling performed by DNA polymerase β, which inserts the correct nucleotide. Finally, DNA ligase seals the nick, restoring the integrity of the DNA strand.
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    Potential of in vitro microelectrode arrays in Alzheimer’s disease research
    Aoife O’Connell, Andrea Kwakowsky
    2026, 21 (5):  1993-1994.  doi: 10.4103/NRR.NRR-D-24-01582
    Abstract ( 73 )   PDF (1298KB) ( 38 )   Save
    Alzheimer ’s disease (AD) is a progressive neurodegenerative disorder and is the most prominent cause of dementia. In 2019, over 57.4 million people were living with AD and other dementia subtypes, a number which is expected to increase to over 152.8 million in the next 25 years. This ever-increasing burden has resulted in AD and other neurodegenerative diseases rising to one of the top 10 causes of death globally (O’Connell et al., 2024). The most wellestablished pathological features of AD include brain shrinkage, accumulation of amyloid-β (Aβ) plaques, neurofibrillary tangles, and a disrupted neuronal network (O’Connell et al., 2024). To date, the cause of AD remains relatively elusive. A plethora of evidence has established Aβ at the forefront of AD pathology, however, the specific mechanisms by which this neurotoxic protein results in the debilitating cognitive decline characteristic of AD remains unknown. It is wellaccepted that the excitatory glutamate and cholinergic neurotransmitter systems are severely altered in AD. More recently, evidence has emerged indicating that the disease also affects the inhibitory GABAergic neurotransmitter system (Govindpani et al., 2017; O’Connell et al., 2024). The molecular changes and neuronal loss in these systems disrupt the excitatory/inhibitory balance in the AD brain, potentially contributing to the memory and learning deficits that characterize the condition (Govindpani et al., 2017).
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    Brain insulin resistance and neuropsychiatric symptoms in Alzheimer’s disease: A role for dopamine signaling
    Anastasia Kontogianni, Hongbin Yang, Wenqiang Chen
    2026, 21 (5):  1995-1996.  doi: 10.4103/NRR.NRR-D-25-00281
    Abstract ( 75 )   PDF (2961KB) ( 53 )   Save
    Type 2 diabetes mellitus has central complications: Diabetes, a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion, or impaired insulin signaling, has significant central complications. Type 2 diabetes mellitus (T2DM), the most prevalent type of diabetes, affects more than 38 million individuals in the United States (approximately 1 in 10) and is defined by chronic hyperglycemia and insulin resistance, which refers to a reduced cellular response to insulin. While T2DM is commonly associated with peripheral complications, it also contributes to central complications, including neuropsychiatric symptoms (NPS) and cognitive decline (Chen et al., 2022), significantly accelerating the progression to Alzheimer’s disease (AD) and related dementias. At the core of these effects lies brain insulin resistance (BIR), a disruption in insulin signaling within the central nervous system that can occur even in individuals without diabetes (Chen et al., 2022).
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    Unraveling the missing heritability of amyotrophic lateral sclerosis: Should we focus more on copy number variations?
    Maria Guarnaccia, Valentina La Cognata, Giulia Gentile, Giovanna Morello, Sebastiano Cavallaro
    2026, 21 (5):  1997-1998.  doi: 10.4103/NRR.NRR-D-24-01604
    Abstract ( 68 )   PDF (560KB) ( 20 )   Save
    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons in the brainstem and spinal cord, leading to muscle weakness, paralysis, and respiratory failure (Morgan and Orrell, 2016). Despite identifying many genes associated with ALS risk and pathogenesis, a discrepancy exists between heritability estimates based on familial studies (40%–60%) (Al-Chalabi et al., 2010) and heritability estimates derived from genetic data (5%–10%) (Megat et al., 2023), such as those obtained through GenomeWide Association Studies. This discrepancy, termed “missing heritability,” fuels ongoing debate and likely stems from ALS’s complex genetic architecture, limitations of current genetic research, unidentified genetic and epigenetic factors, environmental influences, random chance, and potential biases in family and twin study heritability estimates (Van Damme, 2018).
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    Potential impact of parasites in the transmission of chronic wasting disease
    Paulina Soto, Rodrigo Morales
    2026, 21 (5):  1999-2000.  doi: 10.4103/NRR.NRR-D-24-01152
    Abstract ( 74 )   PDF (2139KB) ( 32 )   Save
    Chronic wasting disease — a prion disease affecting cervids: Many neurological conditions, including Alzheimer’s and Parkinson’s diseases, amyotrophic lateral sclerosis, frontotemporal dementias, among others, are caused by the accumulation of misfolded proteins in the brain. These diseases affect not only humans, but also animals. Prion diseases are a particular group of diseases among neurodegenerative disorders that can manifest in epidemic proportions in livestock and wild animals. These are fatal neurological conditions caused by the misfolding of a physiologically generated protein, termed cellular prion protein or PrPC , to a pathological isoform referred to as PrPSc (Prusiner, 1991). The events leading to the formation of PrPSc are not fully understood at the molecular level; however, these processes are known to occur either stochastically, be favored by mutations in the prion protein gene (PRNP), or templated by exogenous PrPSc particles. Prion diseases have been observed in various mammals, including humans. In all cases, these diseases are characterized by the progressive degeneration of the brain, leading to alterations in behavior, weight loss, and ultimately culminating in death.
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    Human spinal cord organoids: A powerful tool to redefine gray matter and lower motor neuron pathophysiology in spinal cord injury
    Maria Jose Quezada , Colin K. Franz
    2026, 21 (5):  2001-2002.  doi: 10.4103/NRR.NRR-D-25-00111
    Abstract ( 75 )   PDF (4975KB) ( 56 )   Save
    Human spinal cord organoids (hSCOs) offer a promising platform to study neurotrauma by addressing many limitations of traditional research models. These organoids provide access to human-specific physiological and genetic mechanisms and can be derived from an individual’s somatic cells (e.g., blood or skin). This enables patient-specific paradigms for precision neurotrauma research, particularly relevant to the over 300,000 people in the United States living with chronic effects of spinal cord injury (SCI).
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    Secretase inhibition in Alzheimer’s disease therapeutics reveals functional roles of amyloid-beta42
    Timothy Daly , Bruno P. Imbimbo
    2026, 21 (5):  2003-2005.  doi: 10.4103/NRR.NRR-D-24-01481
    Abstract ( 69 )   PDF (1371KB) ( 22 )   Save
    In the words of the late Sir Colin Blakemore, neurologists have historically sought to infer brain functions in a manner akin to taking a hammer to a computer— analyzing localized anatomical lesions caused by trauma, tumors, or strokes, noting deficits, and inferring what functions certain brain regions may be responsible for. This approach exemplifies a deletion heuristic, where the absence of a specific function reveals insights about the underlying structures or mechanisms responsible for it. By observing what is lost when a particular brain region is damaged, throughout the history of the field, neurologists have pieced together the intricate relationship between anatomy and function.
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    Effects and mechanisms of adipose tissue–derived extracellular vesicles in vascular inflammation and dysfunction
    Daphne Lintsen, Bieke Broux
    2026, 21 (5):  2005-2006.  doi: 10.4103/NRR.NRR-D-24-01619
    Abstract ( 76 )   PDF (699KB) ( 16 )   Save
    Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases, such as multiple sclerosis (MS), Alzheimer ’s disease, and traumatic brain injury. Even for disorders historically unrelated to neuroinflammation, such as Alzheimer ’s disease, it is now shown to precede pathological protein aggregations. A common factor in these neurodegenerative diseases is activation of brain resident immune cells, as well as breakdown of the blood–brain barrier (BBB), which consecutively causes infiltration of peripheral immune cells, leading to neuronal damage and dysfunction. The integrity of the BBB, a biological barrier between the blood and the central nervous system, therefore plays a crucial role in regulating neuroinflammation. The BBB primarily consists of endothelial cells (ECs) that are tightly connected by tight junction proteins, astrocyte-end feet, and pericytes, conjunctively restricting the infiltration of immune cells and unnecessary biological molecules into the brain. BBB disruption, marked by the loss of structural integrity and upregulation of adhesion molecules and chemokines on the microvascular ECs, leads to infiltrating immune cells in the brain, driving neuroinflammation (Naegele and Martin, 2014).
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    A research perspective on sphingolipid metabolism and myalgic encephalomyelitis/chronic fatigue syndrome
    Junhua Xiao
    2026, 21 (5):  2007-2008.  doi: 10.4103/NRR.NRR-D-24-01506
    Abstract ( 86 )   PDF (445KB) ( 25 )   Save
    Myalgic encephalomyelitis/chronic fatigue syndrome–an insidious disease: The recent COVID-19 pandemic has brought substantial attention to the overlapping symptoms between long COVID and myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS), a chronic and poorly understood neurological disorder (Shankar et al., 2024). The prevalence of ME/CFS is estimated to be over 2 million in the United States (No authors listed, 2015). People with ME/CFS often report prolonged fatigue, chronic or intermittent pain syndromes, autonomic abnormalities, post-exertional malaise, cognitive impairment, and reduced quality of life over an enduring period, many of which do not fully recover from this clinical condition (No authors listed, 2015). Furthermore, the condition is marked by considerable heterogeneity in its clinical definitions and the absence of a definitive diagnostic test, complicating both diagnosis and treatment. Because physicians often struggle to recognize the condition of ME/CFS and form a diagnosis, many individuals are never diagnosed hence the actual number would be substantially higher, posing additional complexity in developing evidence-based therapies for ME/CFS.
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    Role of calcium homeostasis in retinal ganglion cell degeneration
    Sean McCracken, Philip R. Williams
    2026, 21 (5):  2009-2010.  doi: 10.4103/NRR.NRR-D-24-01651
    Abstract ( 75 )   PDF (441KB) ( 12 )   Save
    Calcium (Ca2+) is a key intracellular messenger involved in a variety of cellular functions. Intracellular Ca2+ dysregulation drives neuron cell death in multiple degenerative diseases and traumatic conditions. Retinal ganglion cell (RGC) degeneration occurs in blinding diseases such as glaucoma and other optic neuropathies. Ca2+ function in RGCs has been primarily studied regarding its association with neuronal activity. However, the role of RGC Ca2+ homeostasis and its dysregulation following degeneration is less clear. Here, we describe recent findings using rodent models of RGC degeneration that suggest a role for Ca2+ homeostasis in RGC loss and neuroprotection.
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    Differential plasticity of excitatory and inhibitory reticulospinal fibers after spinal cord injury: Implication for recovery
    Rozaria Jeleva, Carmen Denecke Muhr, Alina P. Liebisch, Florence M. Bareyre
    2026, 21 (5):  2011-2020.  doi: 10.4103/NRR.NRR-D-24-01060
    Abstract ( 87 )   PDF (3672KB) ( 36 )   Save
    The remodeling of axonal connections following injury is an important feature driving functional recovery. The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory fibers. While the reticulospinal tract has been shown to be particularly prone to axonal growth and plasticity following injuries of the spinal cord, the differential capacities of excitatory and inhibitory fibers for plasticity remain unclear. As adaptive axonal plasticity involves a sophisticated interplay between excitatory and inhibitory input, we investigated in this study the plastic potential of glutamatergic (vGlut2) and GABAergic (vGat) fibers originating from the gigantocellular nucleus and the lateral paragigantocellular nucleus, two nuclei important for locomotor function. Using a combination of viral tracing, chemogenetic silencing, and AI-based kinematic analysis, we investigated plasticity and its impact on functional recovery within the first 3 weeks following injury, a period prone to neuronal remodeling. We demonstrate that, in this time frame, while vGlut2-positive fibers within the gigantocellular and lateral paragigantocellular nuclei rewire significantly following cervical spinal cord injury, vGat-positive fibers are rather unresponsive to injury. We also show that the acute silencing of excitatory axonal fibers which rewire in response to lesions of the spinal cord triggers a worsening of the functional recovery. Using kinematic analysis, we also pinpoint the locomotion features associated with the gigantocellular nucleus or lateral paragigantocellular nucleus during functional recovery. Overall, our study increases the understanding of the role of the gigantocellular and lateral paragigantocellular nuclei during functional recovery following spinal cord injury.
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    Lnc_011797 promotes ferroptosis and aggravates white matter lesions
    Xiang Xu, Yu Sun, Xiaoyan Zhu, Shiyin Ma, Jin Wei, Chang He, Jing Chen, Xudong Pan
    2026, 21 (5):  2021-2030.  doi: 10.4103/NRR.NRR-D-24-00676
    Abstract ( 90 )   PDF (13283KB) ( 10 )   Save
    Recent evidence suggests that ferroptosis plays a crucial role in the occurrence and development of white matter lesions. However, the mechanisms and regulatory pathways involved in ferroptosis within white matter lesions remain unclear. Long non-coding RNAs (lncRNAs) have been shown to influence the occurrence and development of these lesions. We previously identified lnc_011797 as a biomarker of white matter lesions by high-throughput sequencing. To investigate the mechanism by which lnc_011797 regulates white matter lesions, we established subjected human umbilical vein endothelial cells to oxygenglucose deprivation to simulate conditions associated with white matter lesions. The cells were transfected with lnc_011797 overexpression or knockdown lentiviruses. Our findings indicate that lnc_011797 promoted ferroptosis in these cells, leading to the formation of white matter lesions. Furthermore, lnc_011797 functioned as a competitive endogenous RNA (ceRNA) for miR-193b-3p, thereby regulating the expression of WNK1 and its downstream ferroptosis-related proteins. To validate the role of lnc_011797 in vivo, we established a mouse model of white matter lesions through bilateral common carotid artery stenosis. The results from this model confirmed that lnc_011797 regulates ferroptosis via WNK1 and promotes the development of white matter lesions. These findings clarify the mechanism by which lncRNAs regulate white matter lesions, providing a new target for the diagnosis and treatment of white matter lesions.
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    Magnetic resonance imaging tracing of superparamagnetic iron oxide nanoparticle–labeled mesenchymal stromal cells for repairing spinal cord injury
    Xiaoli Mai, Yuanyuan Xie, Zhichong Wu, Junting Zou, Jiacheng Du, Yunpeng Shen, Hao Liu, Bo Chen, Mengxia Zhu, Jiong Shi, Yang Chen, Bing Zhang, Zezhang Zhu, Bin Wang, Ning Gu
    2026, 21 (5):  2031-2039.  doi: 10.4103/NRR.NRR-D-24-00431
    Abstract ( 179 )   PDF (20710KB) ( 16 )   Save
    Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases. However, the biological characteristics of transplanted mesenchymal stromal cells in humans remain unclear, including cell viability, distribution, migration, and fate. Conventional cell tracing methods cannot be used in the clinic. The use of superparamagnetic iron oxide nanoparticles as contrast agents allows for the observation of transplanted cells using magnetic resonance imaging. In 2016, the National Medical Products Administration of China approved a new superparamagnetic iron oxide nanoparticle, Ruicun, for use as a contrast agent in clinical trials. In the present study, an acute hemi-transection spinal cord injury model was established in beagle dogs. The injury was then treated by transplantation of Ruicun-labeled mesenchymal stromal cells. The results indicated that Ruicunlabeled mesenchymal stromal cells repaired damaged spinal cord fibers and partially restored neurological function in animals with acute spinal cord injury. T2*-weighted imaging revealed low signal areas on both sides of the injured spinal cord. The results of quantitative susceptibility mapping with ultrashort echo time sequences indicated that Ruicun-labeled mesenchymal stromal cells persisted stably within the injured spinal cord for over 4 weeks. These findings suggest that magnetic resonance imaging has the potential to effectively track the migration of Ruicun-labeled mesenchymal stromal cells and assess their ability to repair spinal cord injury.
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    Tracing motor neurons and primary sensory afferents of the monkey spinal cord with cholera toxin subunit B
    Ziyu He, Zhixian Liu, Wenjie Xu, Ruoying Zhang, Shu Fan, Wei Wang, Xiaolong Zheng
    2026, 21 (5):  2040-2049.  doi: 10.4103/NRR.NRR-D-24-00995
    Abstract ( 90 )   PDF (15026KB) ( 13 )   Save
    Nonhuman primates are increasingly being used as animal models in neuroscience research. However, efficient neuronal tracing techniques for labeling motor neurons and primary sensory afferents in the monkey spinal cord are lacking. Here, by injecting the cholera toxin B subunit into the sciatic nerve of a rhesus monkey, we successfully labeled the motor neurons and primary sensory afferents in the lumbar and sacralspinal cord. Labeled alpha motor neurons were located in lamina IX of the L6–S1 segments, which innervate both flexors and extensors. The labeled primary sensory afferents were mainly myelinated Aβ fibers that terminated mostly in laminae I and II of the L4–L7 segments. Together with the labeled proprioceptive afferents, the primary sensory afferents formed excitatory synapses with multiple types of spinal neurons. In summary, our methods successfully traced neuronal connections in the monkey spinal cord and can be used in spinal cord studies when nonhuman primates are used.
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    Induced pluripotent stem cell–derived mesenchymal stem cells enhance acellular nerve allografts to promote peripheral nerve regeneration by facilitating angiogenesis
    Fan-Qi Meng, Chao-Chao Li, Wen-Jing Xu, Jun-Hao Deng, Yan-Jun Guan, Tie-Yuan Zhang, Bo-Yao Yang, Jian Zhang, Xiang-Ling Li, Feng Han, Zhi-Qi Ren, Shuai Xu, Yan Liang, Wen Jiang, Jiang Peng, Yu Wang, Hai-Ying Liu
    2026, 21 (5):  2050-2059.  doi: 10.4103/NRR.NRR-D-22-00311
    Abstract ( 83 )   PDF (9869KB) ( 27 )   Save
    Previous research has demonstrated the feasibility of repairing nerve defects through acellular allogeneic nerve grafting with bone marrow mesenchymal stem cells. However, adult tissue–derived mesenchymal stem cells encounter various obstacles, including limited tissue sources, invasive acquisition methods, cellular heterogeneity, purification challenges, cellular senescence, and diminished pluripotency and proliferation over successive passages. In this study, we used induced pluripotent stem cell-derived mesenchymal stem cells, known for their self-renewal capacity, multilineage differentiation potential, and immunomodulatory characteristics. We used induced pluripotent stem cell-derived mesenchymal stem cells in conjunction with acellular nerve allografts to address a 10 mm-long defect in a rat model of sciatic nerve injury. Our findings reveal that induced pluripotent stem cell-derived mesenchymal stem cells exhibit survival for up to 17 days in a rat model of peripheral nerve injury with acellular nerve allograft transplantation. Furthermore, the combination of acellular nerve allograft and induced pluripotent stem cell-derived mesenchymal stem cells significantly accelerates the regeneration of injured axons and improves behavioral function recovery in rats. Additionally, our in vivo and in vitro experiments indicate that induced pluripotent stem cell-derived mesenchymal stem cells play a pivotal role in promoting neovascularization. Collectively, our results suggest the potential of acellular nerve allografts with induced pluripotent stem cell-derived mesenchymal stem cells to augment nerve regeneration in rats, offering promising therapeutic strategies for clinical translation.
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    Small extracellular vesicles derived from hair follicle neural crest stem cells enhance perineurial cell proliferation and migration via the TGF-β/SMAD/HAS2 pathway
    Yiming Huo, Bing Xiao, Haojie Yu, Yang Xu, Jiachen Zheng, Chao Huang, Ling Wang, Haiyan Lin, Jiajun Xu, Pengfei Yang, Fang Liu
    2026, 21 (5):  2060-2072.  doi: 10.4103/NRR.NRR-D-25-00127
    Abstract ( 128 )   PDF (11857KB) ( 15 )   Save
    Peripheral nerve defect repair is a complex process that involves multiple cell types; perineurial cells play a pivotal role. Hair follicle neural crest stem cells promote perineurial cell proliferation and migration via paracrine signaling; however, their clinical applications are limited by potential risks such as tumorigenesis and xenogeneic immune rejection, which are similar to the risks associated with other stem cell transplantations. The present study therefore focuses on small extracellular vesicles derived from hair follicle neural crest stem cells, which preserve the bioactive properties of the parent cells while avoiding the transplantation-associated risks. In vitro, small extracellular vesicles derived from hair follicle neural crest stem cells significantly enhanced the proliferation, migration, tube formation, and barrier function of perineurial cells, and subsequently upregulated the expression of tight junction proteins. Furthermore, in a rat model of sciatic nerve defects bridged with silicon tubes, treatment with small extracellular vesicles derived from hair follicle neural crest stem cells resulted in higher tight junction protein expression in perineurial cells, thus facilitating neural tissue regeneration. At 10 weeks post-surgery, rats treated with small extracellular vesicles derived from hair follicle neural crest stem cells exhibited improved nerve function recovery and reduced muscle atrophy. Transcriptomic and microRNA analyses revealed that small extracellular vesicles derived from hair follicle neural crest stem cells deliver miR-21-5p, which inhibits mothers against decapentaplegic homolog 7 expression, thereby activating the transforming growth factor-β/mothers against decapentaplegic homolog signaling pathway and upregulating hyaluronan synthase 2 expression, and further enhancing tight junction protein expression. Together, our findings indicate that small extracellular vesicles derived from hair follicle neural crest stem cells promote the proliferation, migration, and tight junction protein formation of perineurial cells. These results provide new insights into peripheral nerve regeneration from the perspective of perineurial cells, and present a novel approach for the clinical treatment of peripheral nerve defects.
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    R-28 cell-derived extracellular vesicles protect retinal ganglion cells in glaucoma
    Esmahan Durmaz, Maryam Esmaeili, Philip Lewis, Gloria Cimaglia, Aled Clayton, Ben Mead
    2026, 21 (5):  2073-2080.  doi: 10.4103/NRR.NRR-D-24-00709
    Abstract ( 110 )   PDF (7763KB) ( 18 )   Save
    Glaucoma is characterized by chronic progressive optic nerve damage and retinal ganglion cell death. Although extensive research has been conducted on neuroprotection for retinal ganglion cells, there is still no treatment for clinical use. Recent evidence shows that extracellular vesicles isolated from a variety of stem cells are efficacious in retinal ganglion cell neuroprotection. In this study, we tested the novel extracellular vesicle source of the retinal progenitor R-28 cell line in vitro and in vivo. We isolated and characterized extracellular vesicles from R-28 cells and tested their therapeutic efficacy in terms of retinal ganglion cell survival in vitro and in an in vivo glaucoma model, measuring retinal ganglion cell survival and preservation of their axons. Additionally, we tested extracellular vesicles for their neuroprotective capacity in retinal ganglion cells differentiated from human embryonic stem cells. Finally, we investigated miRNA changes in retinal ganglion cells with R-28 extracellular vesicle treatment, and predicted possible pathways that may be modulated. R-28 extracellular vesicles improved retinal ganglion cell survival but failed to preserve axons significantly. Moreover, the results also illustrated the neuroprotection of R-28 extracellular vesicles on human retinal ganglion cells. Finally, we also showed changes in hsa-miRNA-4443, hsa-miRNA-216a-5p, hsa-let-7e-5p, hsa-miRNA-374b-5p, hsa-miRNA-331-3p, and hsa-miRNA-421 expressions, which may have neuroprotective potential on retinal ganglion cell degeneration. This study will pave the way for miRNA and extracellular vesicle-based neuroprotective therapies for glaucoma.
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