| First Author | Choi I | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 1386 |
| PubMed ID | 32170061 | Mgi Jnum | J:286556 |
| Mgi Id | MGI:6401688 | Doi | 10.1038/s41467-020-15119-w |
| Citation | Choi I, et al. (2020) Microglia clear neuron-released alpha-synuclein via selective autophagy and prevent neurodegeneration. Nat Commun 11(1):1386 |
| abstractText | Microglia maintain brain homeostasis by removing neuron-derived components such as myelin and cell debris. The evidence linking microglia to neurodegenerative diseases is growing; however, the precise mechanisms remain poorly understood. Herein, we report a neuroprotective role for microglia in the clearance of neuron-released alpha-synuclein. Neuronal alpha-synuclein activates microglia, which in turn engulf alpha-synuclein into autophagosomes for degradation via selective autophagy (termed synucleinphagy). Synucleinphagy requires the presence of microglial Toll-like receptor 4 (TLR4), which induces transcriptional upregulation of p62/SQSTM1 through the NF-kappaB signaling pathway. Induction of p62, an autophagy receptor, is necessary for the formation of alpha-synuclein/ubiquitin-positive puncta that are degraded by autophagy. Finally, disruption of microglial autophagy in mice expressing human alpha-synuclein promotes the accumulation of misfolded alpha-synuclein and causes midbrain dopaminergic neuron degeneration. Our study thus identifies a neuroprotective function of microglia in the clearance of alpha-synuclein via TLR4-NF-kappaB-p62 mediated synucleinphagy. |
