Table of Content

15 August 2025, Volume 20 Issue 8 Previous Issue   

For Selected:

Download Citations EndNote Reference Manager ProCite BibTeX RefWorks

Toggle Thumbnails

Select

Interaction of major facilitator superfamily domain containing 2A with the blood–brain barrier Yilun Ma, Taiwei Dong, Fei Luan, Juanjuan Yang, Feng Miao, Peifeng Wei 2025, 20 (8):  2133-2152.  doi: 10.4103/NRR.NRR-D-24-00191 Abstract ( 55 )   PDF (5153KB) ( 64 )   Save The functional and structural integrity of the blood–brain barrier is crucial in maintaining homeostasis in the brain microenvironment; however, the molecular mechanisms underlying the formation and function of the blood–brain barrier remain poorly understood. The major facilitator superfamily domain containing 2A has been identified as a key regulator of blood–brain barrier function. It plays a critical role in promoting and maintaining the formation and functional stability of the blood–brain barrier, in addition to the transport of lipids, such as docosahexaenoic acid, across the blood–brain barrier. Furthermore, an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood– brain barrier dysfunction in a variety of neurological diseases; however, little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood–brain barrier. This paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood–brain barrier, including their basic structures and functions, cross-linking between major facilitator superfamily domain containing 2A and the blood– brain barrier, and the in-depth studies on lipid transport and the regulation of blood–brain barrier permeability. This comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood–brain barrier and the research progress to date. This will not only help to elucidate the pathogenesis of neurological diseases, improve the accuracy of laboratory diagnosis, and optimize clinical treatment strategies, but it may also play an important role in prognostic monitoring. In addition, the effects of major facilitator superfamily domain containing 2A on blood–brain barrier leakage in various diseases and the research progress on cross-blood–brain barrier drug delivery are summarized. This review may contribute to the development of new approaches for the treatment of neurological diseases. Related Articles | Metrics

Select

Bidirectional regulation of the brain–gut–microbiota axis following traumatic brain injury Xinyu You, Lin Niu, Jiafeng Fu, Shining Ge, Jiangwei Shi, Yanjun Zhang, Pengwei Zhuang 2025, 20 (8):  2153-2168.  doi: 10.4103/NRR.NRR-D-24-00088 Abstract ( 101 )   PDF (3258KB) ( 78 )   Save Traumatic brain injury is a prevalent disorder of the central nervous system. In addition to primary brain parenchymal damage, the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury; however, the underlying pathogenesis remains unclear, and effective intervention methods are lacking. Intestinal dysfunction is a significant consequence of traumatic brain injury. Being the most densely innervated peripheral tissue in the body, the gut possesses multiple pathways for the establishment of a bidirectional “brain–gut axis” with the central nervous system. The gut harbors a vast microbial community, and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal, hormonal, and immune pathways. A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications. We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury, with a specific focus on the complex biological processes of peripheral nerves, immunity, and microbes triggered by traumatic brain injury, encompassing autonomic dysfunction, neuroendocrine disturbances, peripheral immunosuppression, increased intestinal barrier permeability, compromised responses of sensory nerves to microorganisms, and potential effector nuclei in the central nervous system influenced by gut microbiota. Additionally, we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury. This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the “brain–gut–microbiota axis.” Related Articles | Metrics

Select

Interconnections between diabetic corneal neuropathy and diabetic retinopathy: diagnostic and therapeutic implications Mingyi Yu, Faith Teo En Ning, Chang Liu, Yu-Chi Liu 2025, 20 (8):  2169-2180.  doi: 10.4103/NRR.NRR-D-24-00509 Abstract ( 53 )   PDF (5229KB) ( 38 )   Save Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus. Diabetic corneal neuropathy refers to the progressive damage of corneal nerves. Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature. However, growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit, which includes both the retinal vascular structures and neural tissues. Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening. However, diabetic corneal neuropathy is commonly overlooked and underdiagnosed, leading to severe ocular surface impairment. Several studies have found that these two conditions tend to occur together, and they share similarities in their pathogenesis pathways, being triggered by a status of chronic hyperglycemia. This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy, whether diabetic corneal neuropathy precedes diabetic retinopathy, as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy. We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy. Related Articles | Metrics

Select

Utilizing engineered extracellular vesicles as delivery vectors in the management of ischemic stroke: a special outlook on mitochondrial delivery Jiali Chen, Yiyang Li , Xingping Quan, Jinfen Chen, Yan Han, Li Yang, Manfei Zhou , Greta Seng Peng Mok, Ruibing Wang, Yonghua Zhao 2025, 20 (8):  2181-2198.  doi: 10.4103/NRR.NRR-D-24-00243 Abstract ( 103 )   PDF (1570KB) ( 425 )   Save Ischemic stroke is a secondary cause of mortality worldwide, imposing considerable medical and economic burdens on society. Extracellular vesicles, serving as natural nanocarriers for drug delivery, exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke. However, the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency. By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles, their delivery efficacy may be greatly improved. Furthermore, previous studies have indicated that microvesicles, a subset of large-sized extracellular vesicles, can transport mitochondria to neighboring cells, thereby aiding in the restoration of mitochondrial function post-ischemic stroke. Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components, such as proteins or deoxyribonucleic acid, or their sub-components, for extracellular vesicle–based ischemic stroke therapy. In this review, we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies. Given the complex facets of treating ischemic stroke, we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process. Moreover, given the burgeoning interest in mitochondrial delivery, we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy. Related Articles | Metrics

Select

Neuroprotective potential for mitigating ischemiareperfusion-induced damage Zi Ye, Runqing Liu, Hangxing Wang, Aizhen Zuo, Cen Jin, Nan Wang, Huiqi Sun, Luqian Feng, Hua Yang 2025, 20 (8):  2199-2217.  doi: 10.4103/NRR.NRR-D-23-01985 Abstract ( 134 )   PDF (19909KB) ( 18 )   Save Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient’s condition; this phenomenon is known as cerebral ischemia-reperfusion injury. Current studies have elucidated the neuroprotective role of the sirtuin protein family (Sirtuins) in modulating cerebral ischemia-reperfusion injury. However, the potential of utilizing it as a novel intervention target to influence the prognosis of cerebral ischemia-reperfusion injury requires additional exploration. In this review, the origin and research progress of Sirtuins are summarized, suggesting the involvement of Sirtuins in diverse mechanisms that affect cerebral ischemia-reperfusion injury, including inflammation, oxidative stress, blood–brain barrier damage, apoptosis, pyroptosis, and autophagy. The therapeutic avenues related to Sirtuins that may improve the prognosis of cerebral ischemia-reperfusion injury were also investigated by modulating Sirtuins expression and affecting representative pathways, such as nuclear factor-kappa B signaling, oxidative stress mediated by adenosine monophosphate-activated protein kinase, and the forkhead box O. This review also summarizes the potential of endogenous substances, such as RNA and hormones, drugs, dietary supplements, and emerging therapies that regulate Sirtuins expression. This review also reveals that regulating Sirtuins mitigates cerebral ischemia-reperfusion injury when combined with other risk factors. While Sirtuins show promise as a potential target for the treatment of cerebral ischemiareperfusion injury, most recent studies are based on rodent models with circadian rhythms that are distinct from those of humans, potentially influencing the efficacy of Sirtuinstargeting drug therapies. Overall, this review provides new insights into the role of Sirtuins in the pathology and treatment of cerebral ischemia-reperfusion injury. Related Articles | Metrics

Select

Diabetic peripheral neuropathy and neuromodulation techniques: a systematic review of progress and prospects Rahul Mittal, Keelin McKenna, Grant Keith, Evan McKenna, Joana R. N. Lemos, Jeenu Mittal, Khemraj Hirani 2025, 20 (8):  2218-2230.  doi: 10.4103/NRR.NRR-D-24-00270 Abstract ( 82 )   PDF (4892KB) ( 42 )   Save Neuromodulation for diabetic peripheral neuropathy represents a significant area of interest in the management of chronic pain associated with this condition. Diabetic peripheral neuropathy, a common complication of diabetes, is characterized by nerve damage due to high blood sugar levels that lead to symptoms, such as pain, tingling, and numbness, primarily in the hands and feet. The aim of this systematic review was to evaluate the efficacy of neuromodulatory techniques as potential therapeutic interventions for patients with diabetic peripheral neuropathy, while also examining recent developments in this domain. The investigation encompassed an array of neuromodulation methods, including frequency rhythmic electrical modulated systems, dorsal root ganglion stimulation, and spinal cord stimulation. This systematic review suggests that neuromodulatory techniques may be useful in the treatment of diabetic peripheral neuropathy. Understanding the advantages of these treatments will enable physicians and other healthcare providers to offer additional options for patients with symptoms refractory to standard pharmacologic treatments. Through these efforts, we may improve quality of life and increase functional capacity in patients suffering from complications related to diabetic neuropathy. Related Articles | Metrics

Select

C–C motif chemokine ligand 2/C–C motif chemokine receptor 2 pathway as a therapeutic target and regulatory mechanism for spinal cord injury Xiangzi Wang, Xiaofei Niu, Yingkai Wang, Yang Liu, Cheng Yang, Xuyi Chen, Zhongquan Qi 2025, 20 (8):  2231-2244.  doi: 10.4103/NRR.NRR-D-24-00119 Abstract ( 116 )   PDF (4245KB) ( 63 )   Save Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage. The expression of the C–C motif chemokine ligand 2/C–C motif chemokine receptor 2 axis exhibits significant differences before and after injury. Recent studies have revealed that the C–C motif chemokine ligand 2/C–C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury, suggesting that this axis is a novel target and regulatory control point for treatment. This review comprehensively examines the therapeutic strategies targeting the C–C motif chemokine ligand 2/C–C motif chemokine receptor 2 axis, along with the regenerative and repair mechanisms linking the axis to spinal cord injury. Additionally, we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C–C motif chemokine ligand 2/ C–C motif chemokine receptor 2 axis. This review primarily elaborates on therapeutic strategies that target the C–C motif chemokine ligand 2/C–C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs, along with the approaches used to exploit new therapeutic targets within the C–C motif chemokine ligand 2/C–C motif chemokine receptor 2 axis and the development of targeted drugs. Nevertheless, there are presently no clinical studies relating to spinal cord injury that are focusing on the C–C motif chemokine ligand 2/C–C motif chemokine receptor 2 axis. This review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.  Related Articles | Metrics

Select

Neuronal regulated cell death in aging-related neurodegenerative diseases: key pathways and therapeutic potentials Run Song, Shiyi Yin, Jiannan Wu, Junqiang Yan 2025, 20 (8):  2245-2263.  doi: 10.4103/NRR.NRR-D-24-00025 Abstract ( 138 )   PDF (1900KB) ( 321 )   Save Regulated cell death (such as apoptosis, necroptosis, pyroptosis, autophagy, cuproptosis, ferroptosis, disulfidptosis) involves complex signaling pathways and molecular effectors, and has been proven to be an important regulatory mechanism for regulating neuronal aging and death. However, excessive activation of regulated cell death may lead to the progression of aging-related diseases. This review summarizes recent advances in the understanding of seven forms of regulated cell death in age-related diseases. Notably, the newly identified ferroptosis and cuproptosis have been implicated in the risk of cognitive impairment and neurodegenerative diseases. These forms of cell death exacerbate disease progression by promoting inflammation, oxidative stress, and pathological protein aggregation. The review also provides an overview of key signaling pathways and crosstalk mechanisms among these regulated cell death forms, with a focus on ferroptosis, cuproptosis, and disulfidptosis. For instance, FDX1 directly induces cuproptosis by regulating copper ion valency and dihydrolipoamide S-acetyltransferase aggregation, while copper mediates glutathione peroxidase 4 degradation, enhancing ferroptosis sensitivity. Additionally, inhibiting the Xc- transport system to prevent ferroptosis can increase disulfide formation and shift the NADP+ /NADPH ratio, transitioning ferroptosis to disulfidptosis. These insights help to uncover the potential connections among these novel regulated cell death forms and differentiate them from traditional regulated cell death mechanisms. In conclusion, identifying key targets and their crosstalk points among various regulated cell death pathways may aid in developing specific biomarkers to reverse the aging clock and treat age-related neurodegenerative conditions. Related Articles | Metrics

Select

Glycolytic dysregulation in Alzheimer’s disease: unveiling new avenues for understanding pathogenesis and improving therapy You Wu, Lijie Yang, Wanrong Jiang, Xinyuan Zhang, Zhaohui Yao 2025, 20 (8):  2264-2278.  doi: 10.4103/NRR.NRR-D-24-00190 Abstract ( 203 )   PDF (3633KB) ( 122 )   Save Alzheimer’s disease poses a significant global health challenge owing to the progressive cognitive decline of patients and absence of curative treatments. The current therapeutic strategies, primarily based on cholinesterase inhibitors and N-methyl-Daspartate receptor antagonists, offer limited symptomatic relief without halting disease progression, highlighting an urgent need for novel research directions that address the key mechanisms underlying Alzheimer’s disease. Recent studies have provided insights into the critical role of glycolysis, a fundamental energy metabolism pathway in the brain, in the pathogenesis of Alzheimer’s disease. Alterations in glycolytic processes within neurons and glial cells, including microglia, astrocytes, and oligodendrocytes, have been identified as significant contributors to the pathological landscape of Alzheimer’s disease. Glycolytic changes impact neuronal health and function, thus offering promising targets for therapeutic intervention. The purpose of this review is to consolidate current knowledge on the modifications in glycolysis associated with Alzheimer’s disease and explore the mechanisms by which these abnormalities contribute to disease onset and progression. Comprehensive focus on the pathways through which glycolytic dysfunction influences Alzheimer’s disease pathology should provide insights into potential therapeutic targets and strategies that pave the way for groundbreaking treatments, emphasizing the importance of understanding metabolic processes in the quest for clarification and management of Alzheimer’s disease. Related Articles | Metrics

Select

Decoding molecular mechanisms: brain aging and Alzheimer’s disease Mahnoor Hayat, Rafay Ali Syed, Hammad Qaiser, Mohammad Uzair, Khalid Al-Regaiey, Roaa Khallaf, Lubna Abdullah Mohammed Albassam, Imdad Kaleem, Xueyi Wang, Ran Wang, Mehwish S. Bhatti, Shahid Bashir 2025, 20 (8):  2279-2299.  doi: 10.4103/NRR.NRR-D-23-01403 Abstract ( 99 )   PDF (3574KB) ( 118 )   Save The complex morphological, anatomical, physiological, and chemical mechanisms within the aging brain have been the hot topic of research for centuries. The aging process alters the brain structure that affects functions and cognitions, but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders, such as Alzheimer’s disease. Beyond these observable, mild morphological shifts, significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain. Understanding these changes is important for maintaining cognitive health, especially given the increasing prevalence of age-related conditions that affect cognition. This review aims to explore the age-induced changes in brain plasticity and molecular processes, differentiating normal aging from the pathogenesis of Alzheimer’s disease, thereby providing insights into predicting the risk of dementia, particularly Alzheimer’s disease. Related Articles | Metrics

Select

Neurocircuit regeneration by extracellular matrix reprogramming Shengzhang Su , Ian N. Levasseur , Kimberly M. Alonge 2025, 20 (8):  2300-2301.  doi: 10.4103/NRR.NRR-D-24-00506 Abstract ( 64 )   PDF (3336KB) ( 33 )   Save The brain’s extracellular matrix (ECM), which is comprised of protein and glycosaminoglycan (GAG) scaffolds, constitutes 20%–40% of the human brain and is considered one of the largest influencers on brain cell functioning (Soles et al., 2023). Synthesized by neural and glial cells, the brain’s ECM regulates a myriad of homeostatic cellular processes, including neuronal plasticity and firing (Miyata et al., 2012), cation buffering (Morawski et al., 2015), and glia–neuron interactions (Anderson et al., 2016). Considering the diversity of functions, dynamic remodeling of the brain’s ECM indicates that this understudied medium is an active participant in both normal physiology and neurological diseases. Related Articles | Metrics

Select

Central role of altered phosphodiesterase 2-dependent signaling in the pathophysiology of cognition-based brain disorders Asma Boulksibat , Alessandra Tempio , Barbara Bardoni 2025, 20 (8):  2302-2303.  doi: 10.4103/NRR.NRR-D-24-00588 Abstract ( 37 )   PDF (788KB) ( 19 )   Save The second messengers 3′,5′-cyclic adenosine monophosphate (cAMP) and 3′,5′-cyclic guanosine monophosphate (cGMP) modulate molecular pathways that are involved in a large variety of cellular processes. In the brain, these processes include neurogenesis, neuronal differentiation, activation and function of microglia, and synaptic plasticity, finally resulting in memory formation. All this implies that the homeostasis of these two molecules must be tightly regulated both at their synthesis—that is catalyzed by adenylate/ guanylate cyclase—and at their degradation by phosphodiesterases (PDE). The PDE family is composed of 11 subfamilies of proteins that are all expressed in the brain at different levels (Delhaye et al., 2021). Related Articles | Metrics

Select

Deciphering the mechanobiology of microglia in traumatic brain injury with advanced microsystems Anthony Procès, Sylvain Gabriele 2025, 20 (8):  2304-2306.  doi: 10.4103/NRR.NRR-D-24-00371 Abstract ( 42 )   PDF (5849KB) ( 28 )   Save Advanced microsystems in traumatic brain injury research: Traumatic brain injury (TBI) results from a mechanical insult to the brain, leading to neuronal and axonal damage and subsequently causing a secondary injury. Within minutes of TBI, a neuroinflammatory response is triggered, driven by intricate molecular and cellular inflammatory processes. The temporal progression of TBI events has been investigated using animal models, human surgical and post-mortem tissue samples, and the analysis of cerebrospinal fluid and plasma from TBI patients. However, the complex interplay between injured brain cells remains poorly understood. TBI induces immediate cell death at the site of impact (primary injury), which is dependent on the severity and depth of the injury. Damaged cells release damage-associated molecular patterns, which signal to resident and infiltrating immune cells via pattern recognition receptors. At the injury site, astrocytes, microglia, and damaged neurons secrete cytokines and chemokines, which activate microglia and astrocytes, and recruit peripheral immune cells that penetrate the compromised blood–brain barrier during the acute post-traumatic period (Nespoli et al., 2024). Consequently, TBI is a mechanobiological disorder characterized not only by the dysregulation of neuronal cells but also by a complex interplay of signaling pathways among brain cells. Related Articles | Metrics

Select

Impact of Zika virus non-structural protein mutations on hippocampal damage Larissa M. G. Cassiano, Roney S. Coimbra 2025, 20 (8):  2307-2308.  doi: 10.4103/NRR.NRR-D-24-00493 Abstract ( 31 )   PDF (1317KB) ( 20 )   Save The Zika virus (ZIKV), a member of the Flaviviridae family, attracted worldwide attention for its connection to severe neurological effects, notably microcephaly in newborns, first reported during the 2015 epidemic in Brazil. Yet, its impact goes beyond fetal and neonatal abnormalities, also affecting the central nervous system (CNS) in both children and adults, leading to enduring cognitive and behavioral impairments Related Articles | Metrics

Select

In vivo direct neuronal conversion as a therapeutic strategy for ischemic stroke Takashi Irie, Taito Matsuda 2025, 20 (8):  2309-2310.  doi: 10.4103/NRR.NRR-D-24-00545 Abstract ( 41 )   PDF (605KB) ( 5 )   Save Stroke causes neuronal loss, which ultimately results in persistent neurological dysfunction. Globally, stroke was the third-leading cause of death and disability combined in all ages in 2019, after neonatal disorders and ischemic heart disease. In that year, there were 12.2 million incident strokes, 101 million prevalent strokes, and 143 million disability-adjusted life-years due to stroke. Ischemic stroke constituted 62.4% of all incident strokes in 2019, and showed smaller reductions in age-standardized rates from 1990 to 2019 than intracerebral hemorrhage and subarachnoid hemorrhage (GBD 2019 Stroke Collaborators, 2021). To date, clinical treatments for the hyperacute phase of ischemic stroke are improving, but treatments for subsequent phases remain limited. Related Articles | Metrics

Select

Nucleoside modified mRNA-lipid nanoparticles as a new delivery platform for the repair of the injured spinal cord Krisztián Pajer, Tamás Bellák, Antal Nógrádi 2025, 20 (8):  2311-2312.  doi: 10.4103/NRR.NRR-D-23-01231 Abstract ( 44 )   PDF (2875KB) ( 24 )   Save Spinal cord injury and treatment opportunities: The adult mammalian spinal cord has a very limited capacity for spontaneous regeneration due to various intrinsic molecular and cellular factors. Although the spinal cord neurons have the capacity to regenerate their axons, the expression of growth inhibitory factors, lack or suppression of proper guidance cues, and profound inflammatory responses do not permit successful regeneration (Khyeam et al., 2021). Injury to the spinal cord affects both the long and short ascending and descending pathways thus separating the lower spinal cord segments from the higher motor and sensory centers. The primary physical injury is followed by a cascade of events, called secondary injury. During this phase, inflammation, apoptosis of neuronal and glial cells, glutamate excitotoxicity, disruption of the blood–brain barrier, demyelination of axons, and reactive astrogliosis occur (Silva et al., 2014). Therefore, safe and effective treatments need to be developed to preserve and if possible, regenerate the injured propriospinal and supraspinal tracts and induce favorable changes in the microenvironment of the cord around the lesion. Current therapeutic strategies using stem or progenitor cells, growth factors, or gene therapy via various methods have been attractive approaches to promote neuroprotection and neural regeneration following spinal cord injury (SCI) (Teng, 2019). Out of these many therapeutic ways, stem cells prove to be effective, especially a few stem cell lines, which are able to adapt to the specific needs of the injured cord in order to facilitate neuroprotection and regeneration. Recent evidence suggests that these effective undifferentiated stem cells produce a socalled “lesion-induced secretome” within the cord following transplantation, and they do not need to integrate permanently into the cord to achieve their beneficial effects (Figure 1A; Pajer et al., 2019). However, in cases of other stem cell types, integration into the injured cord is necessary to achieve a therapeutic effect. Related Articles | Metrics

Select

Brain age estimation: premise, promise, and problems Jarrad Perron, Ji Hyun Ko 2025, 20 (8):  2313-2314.  doi: 10.4103/NRR.NRR-D-24-00388 Abstract ( 60 )   PDF (552KB) ( 17 )   Save Premise: The combined effects of modern healthcare practices which prolong lifespan and declining birthrates have created unprecedented changes in age demographics worldwide that are especially pronounced in Japan, South Korea, Europe, and North America. Since old age is the most significant predictor of dementia, global healthcare systems must rise to the challenge of providing care for those with neurodegenerative disorders. This will be a significant global phenomenon since it is predicted that the number of people living with dementia will dramatically increase from 47 million by 2030 to 131 million by 2050 (Wimo and Prince, 2010). Related Articles | Metrics

Select

The loaded matrix: neurotrophinenriched hydrogels for stem cell brain repair in Parkinson’s disease Giulia Comini, Eilis Dowd 2025, 20 (8):  2315-2316.  doi: 10.4103/NRR.NRR-D-24-00586 Abstract ( 49 )   PDF (1381KB) ( 26 )   Save More than 200 years after Parkinson’s disease was first described by the English surgeon whose name would eventually be given to the condition, available treatments remain purely symptomatic, leaving a critical unmet clinical need for a diseasemodifying therapy. One such approach is cellderived brain repair – the transplantation of healthy dopaminergic neurons into the brain to replace those lost from the nigrostriatal pathway throughout the disease. Proof-of-concept for the efficacy of brain repair has amassed from a multitude of both preclinical and clinical trials over several decades. However, this wealth of data is based on the use of human fetuses (after elective termination of pregnancy) as the source of healthy dopaminergic neurons, and this has proven too fraught with ethical and logistical issues to translate into a therapy for patients. While these studies were ongoing, researchers also isolated human embryonic stem cells (ESCs), generated human induced pluripotent stem cells (iPSCs), and developed and refined protocols to convert these to dopaminergic neurons that could be used in place of the human fetal cells. The stem cell era of brain repair is now firmly underway (reviewed in Barker and Bjorklund, 2023) with several clinical trials currently ongoing (including the Kyoto iPSC Trial: UMIN000033564; the BlueRock ECS Trial: NCT04802733; the STEM-PD ESC Trial: NCT05635409; and the S.Biomedics Co. ESC Trial: NCT05887466). Related Articles | Metrics

Select

Mechanisms behind elevated serum levels of plasminogen activator inhibitor-1 in frontotemporal lobar degeneration Francesco Angelucci , Jakub Hort 2025, 20 (8):  2317-2318.  doi: 10.4103/NRR.NRR-D-24-00335 Abstract ( 22 )   PDF (532KB) ( 12 )   Save Frontotemporal lobar degeneration (FTLD) is a form of progressive dementia characterized by degeneration of the frontal and temporal lobes of the brain. This pathology involves a series of cognitive, behavioral, and neurological symptoms that influence personality, decision-making ability, and language. Although it has been recognized for decades, its exact etiology and underlying mechanisms are still not fully understood. In recent years, however, there has been growing interest in research into factors that may contribute to the development and progression of FTLD. Among these, in a recent study, we observed that serum levels of an inhibitor of plasmin synthesis, the plasminogen activator inhibitor-1 (PAI-1), are elevated in FTLD patients with dementia as compared to healthy controls (Angelucci et al., 2024). Furthermore, we observed a negative correlation between PAI-1 serum levels and disease severity measured by MMSE score. Related Articles | Metrics

Select

Carboplatin restores neuronal toxicity in FUS-linked amyotrophic lateral sclerosis Kiyoung Kim 2025, 20 (8):  2319-2320.  doi: 10.4103/NRR.NRR-D-24-00489 Abstract ( 31 )   PDF (527KB) ( 11 )   Save Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig ’s disease, is a progressive neurodegenerative disorder that affects motor neurons in the brain and spinal cord. This leads to muscle weakness, paralysis, and ultimately, respiratory failure (Cha and Kim, 2022). There is currently no cure for ALS. Riluzole, a primary treatment for ALS, has been shown to extend survival by an average of three months. Another drug, Edaravone, has been approved for ALS treatment in some countries; however, its efficacy remains controversial (Cha and Kim, 2022). These drugs target various mechanisms that contribute to neuronal degeneration in ALS, including glutamate excitotoxicity and oxidative stress. Although several studies have attempted to elucidate the underlying mechanisms, there remains an unmet need for more effective therapies to halt or reverse disease progression. Therefore, novel therapeutic strategies are urgently needed. Related Articles | Metrics

Select

Making bridges between preclinical and clinical insights into age-related cognitive decline David VC Brito, Clévio Nóbrega 2025, 20 (8):  2321-2322.  doi: 10.4103/NRR.NRR-D-24-00200 Abstract ( 32 )   PDF (327KB) ( 14 )   Save With people living longer, the societal impact of age-related cognitive decline is becoming more pronounced (Crimmins, 2015). Thus, it is increasingly important to comprehend the cognitive shifts linked to aging – whether they are physiological or pathological. Neurodegenerative disorders are particularly prevalent in older individuals, as the incidence of these conditions is positively correlated with age. However, gene mutations can accelerate the onset of age-related cognitive decline (Pan et al., 2021). Even individuals without dementia, may experience subtle changes in cognition as they grow older, estimated to affect around 20% of older adults (Pais et al., 2020; Chen et al., 2023). Recognizing these cognitive alterations is essential because they can influence an elderly person’s daily functioning and assist in distinguishing between normal aging and illness (Harada et al., 2013). Furthermore, emerging evidence suggests that individuals experiencing agerelated cognitive decline without disease exhibit higher rates of hospitalizations and increased risk for adverse effects (Fogg et al., 2018; Amini et al., 2019). Therefore, it is essential to identify the structural and functional changes responsible for these symptoms. Related Articles | Metrics

Select

Understanding activity of butyrate at a cellular level Prapti Chakraborty, Angela S. Laird 2025, 20 (8):  2323-2324.  doi: 10.4103/NRR.NRR-D-24-00468 Abstract ( 55 )   PDF (1415KB) ( 17 )   Save Butyrate is a short-chain fatty acid of four carbons in length that is a by-product produced by the microbial fermentation of dietary fiber and undigested carbohydrates within the colon. Over the years, butyrate has attracted significant attention due to its diverse roles within cells. These roles include that it serves as an energy source, regulates histone deacetylation, impacts cell development, influences various cellular processes such as apoptosis and autophagy, exerts immunomodulatory functions, and maintains intestinal barrier integrity. Recent studies indicate that butyrate also plays a major role in brain function by strengthening the integrity of blood–brain barrier (BBB), can cross the BBB to exert beneficial effects including modulation of neuroinflammation and neurotransmitter secretion, while acting as a key signal carrier molecule to improve bi-directional communication between the gut and the brain via the gut–brain axis. This perspective aims to summarise butyrate’s intricate cellular mechanisms and their effects on overall health, including neurological well-being. Related Articles | Metrics

Select

Hypidone hydrochloride (YL-0919) ameliorates functional deficits after traumatic brain injury in mice by activating the sigma-1 receptor for antioxidation Yafan Bai, Hui Ma, Yue Zhang, Jinfeng Li , Xiaojuan Hou , Yixin Yang , Guyan Wang, Yunfeng Li 2025, 20 (8):  2325-2336.  doi: 10.4103/NRR.NRR-D-23-01424 Abstract ( 79 )   PDF (8938KB) ( 22 )   Save Traumatic brain injury involves complex pathophysiological mechanisms, among which oxidative stress significantly contributes to the occurrence of secondary injury. In this study, we evaluated hypidone hydrochloride (YL-0919), a self-developed antidepressant with selective sigma-1 receptor agonist properties, and its associated mechanisms and targets in traumatic brain injury. Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema. Next, we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells. Finally, the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist (BD-1047). Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury, while also decreasing neuronal mortality and reversing blood–brain barrier disruption and brain edema. Furthermore, YL-0919 effectively combated oxidative stress both in vivo and in vitro. The protective effects of YL-0919 were partially inhibited by BD-1047. These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress, a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047. YL-0919 may have potential as a new treatment for traumatic brain injury. Related Articles | Metrics

Select

Passive activity enhances residual control ability in patients with complete spinal cord injury Yanqing Xiao , Mingming Gao , Zejia He , Jia Zheng , Hongming Bai , Jia-Sheng Rao, Guiyun Song, Wei Song, Xiaoguang Li 2025, 20 (8):  2337-2347.  doi: 10.4103/NRR.NRR-D-23-01812 Abstract ( 81 )   PDF (2506KB) ( 24 )   Save Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level. However, because of prolonged inactivity, initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway. A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation, as measured by surface electromyography. In this study, we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord injury. Eleven patients with chronic complete thoracic spinal cord injury were recruited. Surface electromyography data from eight major leg muscles were acquired and compared before and after the passive activity protocol. The results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of activation. Although the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity, the difference was not statistically significant. These findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury. Related Articles | Metrics

Select

Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice Mohamed Aghyad Al Kabbani, Christoph Köhler , Hans Zempel 2025, 20 (8):  2348-2360.  doi: 10.4103/NRR.NRR-D-23-01742 Abstract ( 79 )   PDF (11168KB) ( 13 )   Save TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon. TAU is missorted and aggregated in an array of diseases known as tauopathies. Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications, changes of which affect microtubule stability and dynamics, microtubule interaction with other proteins and cellular structures, and mediate recruitment of microtubule-severing enzymes. As impairment of microtubule dynamics causes neuronal dysfunction, we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics. We therefore aimed to study the effects of a disease-causing mutation of TAU (P301L) on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics, to assess whether P301L-TAU causes stability-changing modifications to microtubules. To investigate TAU localization, phosphorylation, and effects on tubulin post-translational modifications, we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons (iNeurons) and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU (pR5 mice). Human neurons expressing the longest TAU isoform (2N4R) with the P301L mutation showed increased TAU phosphorylation at the AT8, but not the p-Ser-262 epitope, and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons. P301L-TAU showed pronounced somatodendritic presence, but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU. P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation, but reduced acetylation, of microtubules compared with non-transgenic littermates. In sum, P301L-TAU results in changes in microtubule PTMs, suggestive of impairment of microtubule stability. This is accompanied by missorting and aggregation of TAU in mice but not in iNeurons. Microtubule PTMs/impairment may be of key importance in tauopathies. Related Articles | Metrics

Select

The cGAS-STING-interferon regulatory factor 7 pathway regulates neuroinflammation in Parkinson’s disease Shengyang Zhou, Ting Li, Wei Zhang, Jian Wu, Hui Hong, Wei Quan, Xinyu Qiao, Chun Cui, Chenmeng Qiao, Weijiang Zhao , Yanqin Shen 2025, 20 (8):  2361-2372.  doi: 10.4103/NRR.NRR-D-23-01684 Abstract ( 107 )   PDF (2888KB) ( 99 )   Save Interferon regulatory factor 7 plays a crucial role in the innate immune response. However, whether interferon regulatory factor 7-mediated signaling contributes to Parkinson’s disease remains unknown. Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine–induced mouse model of Parkinson’s disease and co-localizes with microglial cells. Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype. In addition, siRNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase, tumor necrosis factor α, CD16, CD32, and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1. Taken together, our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase–stimulator of interferon genes–interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson’s disease Related Articles | Metrics

Select

Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases Lifang Zhao, Mingkai Zhang, Qimeng Li, Xuemin Wang, Jie Lu, Ying Han, Yanning Cai 2025, 20 (8):  2373-2381.  doi: 10.4103/NRR.NRR-D-23-01983 Abstract ( 55 )   PDF (1078KB) ( 25 )   Save Several promising plasma biomarker proteins, such as amyloid-β (Aβ), tau, neurofilament light chain, and glial fibrillary acidic protein, are widely used for the diagnosis of neurodegenerative diseases. However, little is known about the long-term stability of these biomarker proteins in plasma samples stored at –80°C. We aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large cohort. Plasma samples from 229 cognitively unimpaired individuals, encompassing healthy controls and those experiencing subjective cognitive decline, as well as 99 patients with cognitive impairment, comprising those with mild cognitive impairment and dementia, were acquired from the Sino Longitudinal Study on Cognitive Decline project. These samples were stored at –80°C for up to 6 years before being used in this study. Our results showed that plasma levels of Aβ42, Aβ40, neurofilament light chain, and glial fibrillary acidic protein were not significantly correlated with sample storage time. However, the level of total tau showed a negative correlation with sample storage time. Notably, in individuals without cognitive impairment, plasma levels of total protein and tau phosphorylated protein threonine 181 (p-tau181) also showed a negative correlation with sample storage time. This was not observed in individuals with cognitive impairment. Consequently, we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage time. Therefore, caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases, such as Alzheimer’s disease. Furthermore, in cohort studies, it is important to consider the impact of storage time on the overall results. Related Articles | Metrics

Select

EZH2-dependent myelination following sciatic nerve injury Hui Zhu, Li Mu, Xi Xu, Tianyi Huang, Ying Wang, Siyuan Xu, Yiting Wang, Wencong Wang, Zhiping Wang, Hongkui Wang, Chengbin Xue 2025, 20 (8):  2382-2394.  doi: 10.4103/NRR.NRR-D-23-02040 Abstract ( 77 )   PDF (10898KB) ( 18 )   Save Demyelination and remyelination have been major focal points in the study of peripheral nerve regeneration following peripheral nerve injury. Notably, the gene regulatory network of regenerated myelin differs from that of native myelin. Silencing of enhancer of zeste homolog 2 (EZH2) hinders the differentiation, maturation, and myelination of Schwann cells in vitro. To further determine the role of EZH2 in myelination and recovery post–peripheral nerve injury, conditional knockout mice lacking Ezh2 in Schwann cells (Ezh2fl/fl;Dhh-Cre and Ezh2fl/fl;Mpz-Cre) were generated. Our results show that a significant proportion of axons in the sciatic nerve of Ezh2-depleted mice remain unmyelinated. This highlights the crucial role of Ezh2 in initiating Schwann cell myelination. Furthermore, we observed that 21 days after inducing a sciatic nerve crush injury in these mice, most axons had remyelinated at the injury site in the control nerve, while Ezh2fl/fl;Mpz-Cre mice had significantly fewer remyelinated axons compared with their wild-type littermates. This suggests that the absence of Ezh2 in Schwann cells impairs myelin formation and remyelination. In conclusion, EZH2 has emerged as a pivotal regulatory factor in the process of demyelination and myelin regeneration following peripheral nerve injury. Modulating EZH2 activity during these processes may offer a promising therapeutic target for the treatment of peripheral nerve injuries. Related Articles | Metrics

Select

Differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia: a double-edged sword María Norte-Muñoz, María Portela-Lomba, Paloma Sobrado-Calvo, Diana Simón, Johnny Di Pierdomenico, Alejandro Gallego-Ortega, Mar Pérez, José M. Cabrera-Maqueda, Javier Sierra, Manuel Vidal-Sanz, María Teresa Moreno-Flores, Marta Agudo-Barriuso 2025, 20 (8):  2395-2407.  doi: 10.4103/NRR.NRR-D-23-01631 Abstract ( 49 )   PDF (35672KB) ( 5 )   Save Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system, including retinal ganglion cell axonal growth through the injured optic nerve. Still, it is unknown whether olfactory ensheathing glia also have neuroprotective properties. Olfactory ensheathing glia express brain-derived neurotrophic factor, one of the best neuroprotectants for axotomized retinal ganglion cells. Therefore, we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush. Olfactory ensheathing glia cells from an established rat immortalized clonal cell line, TEG3, were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments. Anatomical and gene expression analyses were performed. Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex class II molecules. Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days, forming an epimembrane. In axotomized retinas, only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days. In these retinas, microglial anatomical activation was higher than after optic nerve crush alone. In intact retinas, both transplants activated microglial cells and caused retinal ganglion cell death at 21 days, a loss that was higher after allotransplantation, triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression. However, neuroprotection of axotomized retinal ganglion cells did not improve with these treatments. The different neuroprotective properties, different toxic effects, and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables. Related Articles | Metrics

Select

AAV2-PDE6B restores retinal structure and function in the retinal degeneration 10 mouse model of retinitis pigmentosa by promoting phototransduction and inhibiting apoptosis Ruiqi Qiu, Mingzhu Yang, Xiuxiu Jin, Jingyang Liu, Weiping Wang, Xiaoli Zhang, Jinfeng Han, Bo Lei 2025, 20 (8):  2408-2419.  doi: 10.4103/NRR.NRR-D-23-01301 Abstract ( 101 )   PDF (2688KB) ( 62 )   Save Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death. However, there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation. Adeno-associated virus (AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa. The aim of this study was to explore the molecular mechanisms by which AAV2- PDE6B rescues retinal function. To do this, we injected retinal degeneration 10 (rd10) mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark- and light-adapted electroretinogram, optical coherence tomography, and immunofluorescence. Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment, and the results from this analysis were verified by real-time polymerase chain reaction and western blotting. AAV2-PDE6B injection significantly upregulated PDE6β expression, preserved electroretinogram responses, and preserved outer nuclear layer thickness in rd10 mice. Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception, and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice. Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways. Furthermore, the phototransductionrelated proteins Pde6α, Rom1, Rho, Aldh1a1, and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment. Finally, Bax/Bcl-2, p-ERK/ERK, and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment. Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa. Related Articles | Metrics

Select

CNKSR2 interactome analysis indicates its association with the centrosome/microtubule system Lin Yin, Yalan Xu, Jie Mu, Yu Leng, Lei Ma, Yu Zheng, Ruizhi Li, Yin Wang, Peifeng Li, Hai Zhu, Dong Wang, Jing Li 2025, 20 (8):  2420-2432.  doi: 10.4103/NRR.NRR-D-23-01725 Abstract ( 48 )   PDF (15978KB) ( 2 )   Save The protein connector enhancer of kinase suppressor of Ras 2 (CNKSR2), present in both the postsynaptic density and cytoplasm of neurons, is a scaffolding protein with several protein-binding domains. Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders, particularly intellectual disability, although the precise mechanism involved has not yet been fully understood. Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane, thereby influencing synaptic signaling and the morphogenesis of dendritic spines. However, the function of CNKSR2 in the cytoplasm remains to be elucidated. In this study, we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2. Through a combination of bioinformatic analysis and cytological experiments, we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome. We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290. Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2. When we downregulated CNKSR2 expression in mouse neuroblastoma cells (Neuro 2A), we observed significant changes in the expression of numerous centrosomal genes. This manipulation also affected centrosome-related functions, including cell size and shape, cell proliferation, and motility. Furthermore, we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder. Our findings establish a connection between CNKSR2 and the centrosome, and offer new insights into the underlying mechanisms of neurodevelopmental disorders. Related Articles | Metrics