Nature communications, 2020-03, Vol.11 (1), p.1386-1386, Article 1386
2020
Details
- Autor(en) / Beteiligte
- Titel
- Microglia clear neuron-released α-synuclein via selective autophagy and prevent neurodegeneration
- Ist Teil von
- Nature communications, 2020-03, Vol.11 (1), p.1386-1386, Article 1386
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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 α-synuclein. Neuronal α-synuclein activates microglia, which in turn engulf α-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-κB signaling pathway. Induction of p62, an autophagy receptor, is necessary for the formation of α-synuclein/ubiquitin-positive puncta that are degraded by autophagy. Finally, disruption of microglial autophagy in mice expressing human α-synuclein promotes the accumulation of misfolded α-synuclein and causes midbrain dopaminergic neuron degeneration. Our study thus identifies a neuroprotective function of microglia in the clearance of α-synuclein via TLR4-NF-κB-p62 mediated synucleinphagy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-020-15119-wTitel-ID: cdi_doaj_primary_oai_doaj_org_article_666741e7ee464c8c913aa49d57227aa6
- Format
- –
- Schlagworte
- Accumulation, alpha-Synuclein - metabolism, Animals, Autoantigens - metabolism, Autophagy, Autophagy - physiology, Bioaccumulation, Brain, Brain - metabolism, Degeneration, Disease Models, Animal, Disruption, Dopamine receptors, Dopaminergic Neurons - metabolism, Female, HEK293 Cells, Homeostasis, Humans, Mesencephalon, Mesencephalon - metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Microglia, Microglia - metabolism, Microglia - pathology, Myelin, Neurodegeneration, Neurodegenerative diseases, Neurodegenerative Diseases - metabolism, Neuroprotection, NF-kappa B - metabolism, NF-κB protein, Phagocytosis, Phagosomes, Signal Transduction, Synuclein, TLR4 protein, Toll-Like Receptor 4 - metabolism, Toll-like receptors, Transcription, Ubiquitin