Microglia jointly degrade fibrillar alpha-synuclein cargo by distribution through tunneling nanotubes.

ABSTRACT: Microglia are the CNS resident immune cells that react to misfolded proteins through pattern recognition receptor ligation and activation of inflammatory pathways. Here, we studied how microglia handle and cope with α-synuclein (α-syn) fibrils and their clearance. We found that microglia exposed to α-syn establish a cellular network through the formation of F-actin-dependent intercellular connections, which transfer α-syn from overloaded microglia to neighboring naive microglia where the α-syn cargo got rapidly and effectively degraded. Lowering the α-syn burden attenuated the inflammatory profile of microglia and improved their survival. This degradation strategy was compromised in cells carrying the LRRK2 G2019S mutation. We confirmed the intercellular transfer of α-syn assemblies in mic

SUBMITTER: Scheiblich H 

PROVIDER: S-EPMC8527836 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature