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[220609 저널발표] Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease
https://www.nature.com/articles/s41586-023-06120-6#Abs1 2023.06.07 -
[230609 저널발표] Autophagy enables microglia to engage amyloid plaques and prevents microglial senescence
ArticlePublished: 25 May 2023Autophagy enables microglia to engage amyloid plaques and prevents microglial senescenceInsup Choi, Minghui Wang, Seungyeul Yoo, Peng Xu, Steven P. Seegobin, Xianting Li, Xian Han, Qian Wang, Junmin Peng, Bin Zhang & Zhenyu Yue Nature Cell Biology (2023)Cite this article2587 Accesses62 AltmetricMetricsdetailsAbstractDysfunctional autophagy has been implicated in the pathogenesis of Alzheimer’s disease (AD). Previous evidence suggested disruptions of multiple stages of the autophagy-lysosomal pathway in affected neurons. However, whether and how deregulated autophagy in microglia, a cell type with an important link to AD, contributes to AD progression remains elusive. Here we report that autophagy is activated in microglia, particularly of disease-associated microglia surrounding amyloid plaques in AD mouse models. Inhibition of microglial autophagy causes disengagement of microglia from amyloid plaques, suppression of disease-associated microglia, and aggravation of neuropathology in AD mice. Mechanistically, autophagy deficiency promotes senescence-associated microglia as evidenced by reduced proliferation, increased Cdkn1a/p21Cip1, dystrophic morphologies and senescence-associated secretory phenotype. Pharmacological treatment removes autophagy-deficient senescent microglia and alleviates neuropathology in AD mice. Our study demonstrates the protective role of microglial autophagy in regulating the homeostasis of amyloid plaques and preventing senescence; removal of senescent microglia is a promising therapeutic strategy. 2023.06.07