Lysosomal exocytosis releases pathogenic α-synuclein species from neurons in synucleinopathy models.

ABSTRACT: Considerable evidence supports the release of pathogenic aggregates of the neuronal protein α-Synuclein (αSyn) into the extracellular space. While this release is proposed to instigate the neuron-to-neuron transmission and spread of αSyn pathology in synucleinopathies including Parkinson's disease, the molecular-cellular mechanism(s) remain unclear. To study this, we generated a new mouse model to specifically immunoisolate neuronal lysosomes, and established a long-term culture model where αSyn aggregates are produced within neurons without the addition of exogenous fibrils. We show that neuronally generated pathogenic species of αSyn accumulate within neuronal lysosomes in mouse brains and primary neurons. We then find that neurons release these pathogenic αSyn species via SNARE-dependen

SUBMITTER: Xie YX 

PROVIDER: S-EPMC9395532 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature