小胶质细胞
衰老
生物
细胞生物学
α-突触核蛋白
星形胶质细胞
神经退行性变
神经病理学
神经胶质
帕金森病
疾病
病理
神经科学
中枢神经系统
免疫学
医学
炎症
作者
Dinesh Verma,Bo Am Seo,Anurupa Ghosh,Xun Shi,Karina Hernandez-Quijada,Julie K. Andersen,Han Seok Ko,Yong‐Hwan Kim
出处
期刊:Cells
[MDPI AG]
日期:2021-07-05
卷期号:10 (7): 1694-1694
被引量:42
标识
DOI:10.3390/cells10071694
摘要
Emerging evidence indicates that cellular senescence could be a critical inducing factor for aging-associated neurodegenerative disorders. However, the involvement of cellular senescence remains unclear in Parkinson’s disease (PD). To determine this, we assessed the effects of α-synuclein preformed fibrils (α-syn PFF) or 1-methyl-4-phenylpyridinium (MPP+) on changes in cellular senescence markers, employing α-syn PFF treated-dopaminergic N27 cells, primary cortical neurons, astrocytes and microglia and α-syn PFF-injected mouse brain tissues, as well as human PD patient brains. Our results demonstrate that α-syn PFF-induced toxicity reduces the levels of Lamin B1 and HMGB1, both established markers of cellular senescence, in correlation with an increase in the levels of p21, a cell cycle-arrester and senescence marker, in both reactive astrocytes and microglia in mouse brains. Using Western blot and immunohistochemistry, we found these cellular senescence markers in reactive astrocytes as indicated by enlarged cell bodies within GFAP-positive cells and Iba1-positive activated microglia in α-syn PFF injected mouse brains. These results indicate that PFF-induced pathology could lead to astrocyte and/or microglia senescence in PD brains, which may contribute to neuropathology in this model. Targeting senescent cells using senolytics could therefore constitute a viable therapeutic option for the treatment of PD.
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