中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (9): 2594-2595.doi: 10.4103/NRR.NRR-D-24-00659

• 观点:退行性病与再生 • 上一篇    下一篇

阿尔茨海默病中的多聚糖：致病机制和潜在治疗靶点

  

  • 出版日期:2025-09-15 发布日期:2024-12-28

Syndecans in Alzheimer’s disease: pathogenetic mechanisms and potential therapeutic targets

Carmela Rita Balistreri* , Roberto Monastero*   

  1. Cellular, Molecular and Clinical Pathological Laboratory, Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University of Palermo, Palermo, Italy (Balistreri CR) Memory and Parkinson’s disease Center, Policlinico “Paolo Giaccone”, Palermo; Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University of Palermo, Via La Loggia 1, Palermo, Italy (Monastero R)
  • Online:2025-09-15 Published:2024-12-28
  • Contact: Carmela Rita Balistreri, PhD, carmelarita.balistreri@unipa.it; Roberto Monastero, MD, PhD, roberto.monastero@unipa.it.
  • Supported by:
    This article was supported by grants from the Next Generation EU - MUR D.M. 737/2021 - Project PSEBPEHRD - CUP B79J21038330001 (to CRB).

PDF

31

摘要： https://orcid.org/0000-0002-5393-1007 (Carmela Rita Balistreri) https://orcid.org/0000-0002-2829-523X (Roberto Monastero)

Abstract: With increasing age, humans become more susceptible to the onset of neurodegenerative diseases (NDs), and among these, Alzheimer’s disease (AD) is the most frequent (Nicoletti et al., 2023). NDs are primarily characterized by neuronal loss and atrophy, but also by lesions involving the cerebral and/or cardiovascular system (Balistreri, 2021). Lesions such as macroinfarcts, microinfarcts, hemorrhages, white matter lesions, atherosclerosis, and arteriolosclerosis have also been significantly described in the preclinical stages of cognitive impairment characterizing NDs (Mariani et al., 2007). Vascular lesions are described as being characterized by the lifelong accumulation of abnormally activated inflammatory cells and microglia in both brain tissue and vessel walls. This leads to a reduction in cerebral blood flow, causing insufficient energy to the neurons, particularly under conditions of increased cerebral energy demand or vasospasm (Balistreri, 2021). This alteration causes ischemiainduced neuronal apoptosis and necrosis, which can damage brain tissue and cause a range of functional symptoms. In addition, lesions of the inner vessel wall cause endothelial dysfunction, also characterized by alterations in the glycocalyx, which contribute both to the disruption of the blood–brain barrier (BBB) and further reduce cerebral blood flow, causing further damage to neurons with further infiltration of inflammatory cells. All this leads, like a vicious circle, to further neuronal damage with subsequent cortical atrophy and the onset of NDs, first and foremost AD (Balistreri, 2021). This growing evidence suggests the relevance of the vascular role in cognitive impairment and dementia, which needs to be further investigated. Accordingly, we have recently illustrated in a narrative review that the endothelium dysfunction, as well as the dysfunction of its glycocalyx and the related cellular and molecular mechanisms, represent one of the main pathological processes in the onset of NDs (Balistreri et al., 2024). Endothelial cells are, in fact, essential components of the stroma of all tissues and organs, as well as the neurovascular unit (NVU) and BBB. In the latter, endothelial cells, together with microglia cells regulate the transport of nutrients and toxins in the brain, but dysfunctional endothelial cells can also evocate brain inflammation (Balistreri and Monastero, 2023).