α-Synuclein O-GlcNAcylation alters aggregation and toxicity, revealing certain residues as potential inhibitors of Parkinson’s disease

• DOI: 10.1073/pnas.1808845116
• Publication Date: 2019-01-17T02:29:14Z
• Authors: Paul M. Levine; Ana Galesic; Aaron T. Balana; Anne-Laure Mahul-...; Mariana X. Navarro; Cesar A. De Leon; Hilal A. Lashuel; Matthew R. Pratt
• Keywords: Synuclein

Significance Preventing the aggregation of toxic proteins in neurodegenerative diseases is both an important biological function and a potential therapeutic strategy. Here, we examine consequences O-GlcNAcylation on toxicity α-synuclein, aggregating protein Parkinson’s disease. α-Synuclein modified by O-GlcNAc at least nine different positions vivo, but most these modifications are unknown. use synthetic chemistry to prepare six O-GlcNAcylated forms α-synuclein show that they have largely inhibitory, site-specific, effects cellular this protein. These results suggest may be strategy prevent aggregation, which could potentially exploited for treatment.