Structure-function relationship of alpha-synuclein fibrils derived from distinct synucleinopathies

ABSTRACT: The different phenotypic characteristics of Parkinson's disease (PD), Dementia with Lewy Bodies (DLB) and Multiple System atrophy (MSA) are thought to originate from distinct amyloid states of the protein α-Synuclein. Here, using covalent labeling and limited proteolysis-mass spectrometry in vitro and in situ within cells and in patient brain homogenates, we show that pathogenic α-Synuclein from distinct synucleinopathies are structurally different. Further, we discovered disease-specific ubiquitination and turnover profiles for pathogenic α-Synuclein structures, detected molecular pathways responding specifically to uptake of different α-Synuclein fibrillar polymorphs, and identified a subset of the involved proteins as putative interactors of the different α-Synuclein species. Components

SUBMITTER: Tetiana Serdiuk 

PROVIDER: S-SCDT-10_1038-S44320-026-00199-5 | biostudies-other |

REPOSITORIES: biostudies-other