Toxicity of extracellular alpha-synuclein is independent of intracellular alpha-synuclein.

ABSTRACT: Parkinson´s disease (PD) pathology progresses throughout the nervous system. Whereas motor symptoms are always present, there is a high variability in the prevalence of non-motor symptoms. It has been postulated that the progression of the pathology is based on a prion-like disease mechanism partly due to the seeding effect of endocytosed-alpha-synuclein (ASYN) on the endogenous ASYN. Here, we analyzed the role of endogenous ASYN in the progression of PD-like pathology in vivo and in vitro and compared the effect of endocytosed-ASYN as well as paraquat and rotenone on primary enteric, dopaminergic and cortical neurons from wild-type and ASYN-KO mice. Our results show that, in vivo, pathology progression did not occur in the absence of endogenous ASYN. Remarkably, the damage caused by endoc

SUBMITTER: Dening Y 

PROVIDER: S-EPMC9763379 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature