| First Author | Choi I | Year | 2023 |
| Journal | Nat Cell Biol | Volume | 25 |
| Issue | 7 | Pages | 963-974 |
| PubMed ID | 37231161 | Mgi Jnum | J:340859 |
| Mgi Id | MGI:7520972 | Doi | 10.1038/s41556-023-01158-0 |
| Citation | Choi I, et al. (2023) Autophagy enables microglia to engage amyloid plaques and prevents microglial senescence. Nat Cell Biol 25(7):963-974 |
| abstractText | Dysfunctional 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/p21(Cip1), 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. |
