阿尔茨海默病中的细胞衰老:从生理学到病理学。

Cellular senescence in Alzheimer's disease: from physiology to pathology.

机构信息

Department of Pulmonary and Critical Care Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, China.

Laboratory of Exercise and Neurobiology, School of Physical Education and Sports Science, South China Normal University, Guangzhou, 510006, Guangdong, China.

出版信息

Transl Neurodegener. 2024 Nov 20;13(1):55. doi: 10.1186/s40035-024-00447-4.

Abstract

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders, characterized by the accumulation of Aβ and abnormal tau hyperphosphorylation. Despite substantial efforts in development of drugs targeting Aβ and tau pathologies, effective therapeutic strategies for AD remain elusive. Recent attention has been paid to the significant role of cellular senescence in AD progression. Mounting evidence suggests that interventions targeting cellular senescence hold promise in improving cognitive function and ameliorating hallmark pathologies in AD. This narrative review provides a comprehensive summary and discussion of the physiological roles, characteristics, biomarkers, and commonly employed in vivo and in vitro models of cellular senescence, with a particular focus on various cell types in the brain, including astrocytes, microglia, oligodendrocyte precursor cells, neurons, and endothelial cells. The review further delves into factors influencing cellular senescence in AD and emphasizes the significance of targeting cellular senescence as a promising approach for AD treatment, which includes the utilization of senolytics and senomorphics.

摘要

阿尔茨海默病(AD)是最常见的神经退行性疾病之一,其特征是 Aβ 的积累和异常的 tau 过度磷酸化。尽管在开发针对 Aβ 和 tau 病理学的药物方面做出了大量努力,但 AD 的有效治疗策略仍难以捉摸。最近,人们对细胞衰老在 AD 进展中的重要作用给予了关注。越来越多的证据表明,针对细胞衰老的干预措施有望改善认知功能并改善 AD 的标志性病理学。这篇综述性文章全面总结和讨论了细胞衰老的生理作用、特征、生物标志物以及常用的体内和体外模型,特别关注了大脑中的各种细胞类型,包括星形胶质细胞、小胶质细胞、少突胶质前体细胞、神经元和内皮细胞。本文进一步探讨了影响 AD 中细胞衰老的因素,并强调了将细胞衰老作为 AD 治疗的一种有前途的方法的重要性,其中包括使用衰老细胞清除剂和衰老模拟物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b30/11577763/35c0c61e45a2/40035_2024_447_Fig1_HTML.jpg

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