Multiscale measurement of O-GlcNAc changes in Parkinson’s Disease 

Drugs that increase O-GlcNAc have been developed and proceeded into clinical trials. Notably, O-GlcNAc is found on neurodegeneration associated proteins, like tau and α-Syn, and has been shown to inhibit their amyloid aggregation and associated pathology in vitro and in mouse models. However, little is known concerning any differences in O-GlcNAc levels in PD versus healthy brain tissues or whether O-GlcNAc modified α-Syn is excluded from corresponding insoluble inclusions. This project will directly fill in this missing knowledge at the level of the proteome, α-Syn modification levels, and the individual sites of O-GlcNAc on α-Syn. If we find that O-GlcNAc levels on disease relevant proteins are altered and/or that O-GlcNAc is only associated with soluble α-Syn, this information will provide strong supporting evidence to enable data-driven targeting of OGA as a potential therapeutic strategy.

Funder: Michael J. Fox Foundation 

Amount: $638,256 

PI: Robert Wells, Franklin College of Arts and Sciences, Department of Biochemistry and Molecular Biology