A cullin-RING ubiquitin ligase targets exogenous α-synuclein and inhibits Lewy body-like pathology.

ABSTRACT: Parkinson's disease (PD) is a neurological disorder characterized by the progressive accumulation of neuronal α-synuclein (αSyn) inclusions called Lewy bodies. It is believed that Lewy bodies spread throughout the nervous system due to the cell-to-cell propagation of αSyn via cycles of secretion and uptake. Here, we investigated the internalization and intracellular accumulation of exogenous αSyn, two key steps of Lewy body pathogenesis, amplification and spreading. We found that stable αSyn fibrils substantially accumulate in different cell lines upon internalization, whereas αSyn monomers, oligomers, and dissociable fibrils do not. Our data indicate that the uptake-mediated accumulation of αSyn in a human-derived neuroblastoma cell line triggered an adaptive response that involved protei

SUBMITTER: Gerez JA 

PROVIDER: S-EPMC10697662 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature