TNF-α promotes α-synuclein propagation through stimulation of senescence-associated lysosomal exocytosis.

ABSTRACT: Cell-to-cell propagation of α-synuclein is thought to be the underlying mechanism of Parkinson's disease progression. Recent evidence suggests that inflammation plays an important role in the propagation of protein aggregates. However, the mechanism by which inflammation regulates the propagation of aggregates remains unknown. Here, using in vitro cultures, we found that soluble factors secreted from activated microglia promote cell-to-cell propagation of α-synuclein and further showed that among these soluble factors, TNF-α had the most robust stimulatory activity. Treatment of neurons with TNF-α triggered cellular senescence, as shown by transcriptomic analyses demonstrating induction of senescence-associated genes and immunoanalysis of senescence phenotype marker proteins. Interestingly

SUBMITTER: Bae EJ 

PROVIDER: S-EPMC9352737 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature