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神经胶质细胞衰老在阿尔茨海默病中的作用

The Role of Glial Cell Senescence in Alzheimer's Disease.

作者信息

Alshaebi Fadhl, Sciortino Alessia, Kayed Rakez

机构信息

Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, Texas, USA.

Departments of Neurology, Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas, USA.

出版信息

J Neurochem. 2025 Mar;169(3):e70051. doi: 10.1111/jnc.70051.

Abstract

Glial cell senescence, characterized by the irreversible arrest of cell division and a pro-inflammatory secretory phenotype, has emerged as a critical player in the pathogenesis of Alzheimer's disease (ad). While much attention has been devoted to the role of neurons in ad, growing evidence suggests that glial cells, including astrocytes, microglia, and oligodendrocytes, contribute significantly to disease progression through senescence. In this review, we explore the molecular mechanisms underlying glial cell senescence in ad, focusing on the cellular signaling pathways, including DNA damage response and the accumulation of senescence-associated secretory phenotypes (SASP). We also examine how senescent glial cells exacerbate neuroinflammation, disrupt synaptic function, and promote neuronal death in ad. Moreover, we discuss emerging therapeutic strategies aimed at targeting glial cell senescence to mitigate the neurodegenerative processes in ad. By providing a comprehensive overview of current research on glial cell senescence in Alzheimer's disease, this review highlights its potential as a novel therapeutic target in the fight against ad.

摘要

神经胶质细胞衰老,其特征为细胞分裂的不可逆停滞和促炎分泌表型,已成为阿尔茨海默病(AD)发病机制中的关键因素。虽然人们对神经元在AD中的作用给予了很多关注,但越来越多的证据表明,包括星形胶质细胞、小胶质细胞和少突胶质细胞在内的神经胶质细胞通过衰老对疾病进展有显著贡献。在这篇综述中,我们探讨了AD中神经胶质细胞衰老的分子机制,重点关注细胞信号通路,包括DNA损伤反应和衰老相关分泌表型(SASP)的积累。我们还研究了衰老的神经胶质细胞如何加剧神经炎症、破坏突触功能并促进AD中的神经元死亡。此外,我们讨论了旨在靶向神经胶质细胞衰老以减轻AD中神经退行性过程的新兴治疗策略。通过全面概述目前关于阿尔茨海默病中神经胶质细胞衰老的研究,本综述突出了其作为对抗AD的新型治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ed1/11934031/821c2c4d80b5/JNC-169-0-g002.jpg

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