O-GlcNAc forces an α-synuclein amyloid strain with notably diminished seeding and pathology.

ABSTRACT: Amyloid-forming proteins such α-synuclein and tau, which are implicated in Alzheimer's and Parkinson's disease, can form different fibril structures or strains with distinct toxic properties, seeding activities and pathology. Understanding the determinants contributing to the formation of different amyloid features could open new avenues for developing disease-specific diagnostics and therapies. Here we report that O-GlcNAc modification of α-synuclein monomers results in the formation of amyloid fibril with distinct core structure, as revealed by cryogenic electron microscopy, and diminished seeding activity in seeding-based neuronal and rodent models of Parkinson's disease. Although the mechanisms underpinning the seeding neutralization activity of the O-GlcNAc-modified fibrils remain unc

SUBMITTER: Balana AT 

PROVIDER: S-EPMC11062923 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature