Evidence and perspectives of cell senescence in neurodegenerative diseases

• Published in: Biomedicine & pharmacotherapy Vol. 137; p. 111327
• Main Authors: Si, Zizhen, Sun, Linlin, Wang, Xidi
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.05.2021; Elsevier
• Subjects: Alzheimer’s disease; Cell senescence; Multiple sclerosis; Neurodegenerative disease; Parkinson’s disease; Senolytics; Neurodegenerative disease; Cell senescence; Multiple sclerosis; Senolytics; Alzheimer’s disease; Parkinson’s disease
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2021.111327

[Display omitted] •Cell senescence is involved in the occurrence or aggravation of neurodegenerative diseases and cognitive impairments.•Brain cells, including neurons, microglia, astrocytes, oligodendrocytes, and endothelial cells, undergo cell senescence leading to various neurodegenerative diseases.•Senolytic approaches that eliminate both senescent cells and the accompanying SASP may represent novel therapeutic strategies for treating neurodegenerative diseases. Increased life expectancies have significantly increased the number of individuals suffering from geriatric neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The financial cost for current and future patients with these diseases is overwhelming, resulting in substantial economic and societal costs. Unfortunately, most recent high-profile clinical trials for neurodegenerative diseases have failed to obtain efficacious results, indicating that novel approaches are desperately needed to treat these pathologies. Cell senescence, characterized by permanent cell cycle arrest, resistance to apoptosis, mitochondrial alterations, and secretion of senescence-associated secretory phenotype (SASP) components, has been extensively studied in mitotic cells such as fibroblasts, which is considered a hallmark of aging. Furthermore, multiple cell types in the senescent state in the brain, including neurons, microglia, astrocytes, and neural stem cells, have recently been observed in the context of neurodegenerative diseases, suggesting that these senescent cells may play an essential role in the pathological processes of neurodegenerative diseases. Therefore, this review begins by outlining key aspects of cell senescence constitution followed by examining the evidence implicating senescent cells in neurodegenerative diseases. In the final section, we review how cell senescence may be targeted as novel therapeutics to treat pathologies associated with neurodegenerative diseases.