Microglia clear neuron-released α-synuclein via selective autophagy and prevent neurodegeneration

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…

• IS
  Icahn School of Medicine at Mount Sinai
• NI
  National Institutes of Health

  Awards: and P50NS094733, P50NS094733, NS060123
• NI
  National Institute of Neurological Disorders and Stroke

  Awards: P50NS094733, NS060123