Upregulation of Cellular Palmitoylation Mitigates α-Synuclein Accumulation and Neurotoxicity.

ABSTRACT:

Background

Synucleinopathies, including Parkinson's disease (PD), are characterized by α-synuclein (αS) cytoplasmic inclusions. αS-dependent vesicle-trafficking defects are important in PD pathogenesis, but their mechanisms are not well understood. Protein palmitoylation, post-translational addition of the fatty acid palmitate to cysteines, promotes trafficking by anchoring specific proteins to the vesicle membrane. αS itself cannot be palmitoylated as it lacks cysteines, but it binds to membranes, where palmitoylation occurs, via an amphipathic helix. We hypothesized that abnormal αS membrane-binding impairs trafficking by disrupting palmitoylation. Accordingly, we investigated the therapeutic potential of increasing cellular palmitoylation.

Objectives

We asked whether upre

SUBMITTER: Ho GPH 

PROVIDER: S-EPMC8887921 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature