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

ABSTRACT:

Background

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 α-synuclein mutations, no mutations are associated with MSA. We previously 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.

Objective

Here we sought to further interrogate α-synuclein misfolding to identify the structural determinants that contribute to MSA strain biology.

Methods

We engineered a panel of cell lines harbouring both PD-linked and novel mutations designed to identify key residues that facilitate

SUBMITTER: Reis PM 

PROVIDER: S-EPMC11924605 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature