Structurally targeted mutagenesis identifies key residues supporting α -synuclein misfolding in multiple system atrophy.

ABSTRACT: Multiple system atrophy (MSA) and Parkinson's disease (PD) are caused by misfolded α -synuclein spreading throughout the central nervous system. While familial PD is linked to several point mutations in α -synuclein, there are no known mutations associated with MSA. Our previous work investigating differences in α -synuclein misfolding between the two disorders showed that the familial PD mutation E46K inhibits replication of MSA prions both in vitro and in vivo, providing key evidence to support the hypothesis that α -synuclein adopts unique strains in patients. Here, to further interrogate α -synuclein misfolding, we engineered a panel of cell lines harboring both PD-linked and novel mutations designed to identify key residues that facilitate α -synuclein misfolding in MSA.

SUBMITTER: Reis PM 

PROVIDER: S-EPMC11257492 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature