Objective/Rationale:
Alpha Galactosidase A (alpha-Gal A) is an enzyme that is ordinarily responsible for lipid recycling in cells. Researchers have shown how pre-clinical models that lack alpha-Gal A have increased levels of alpha-synuclein, a protein associated with Parkinson’s disease. This project will determine if alpha-Gal A is present at lower levels or has less function in Parkinson’s disease brain, and also if there is a buildup of lipids that are ordinarily degraded by alpha-Gal A.
Project Description:
Brains from control patients and from patients with three different “stages” of Parkinson’s disease grouped by increasing severity of their brain pathology will be obtained from the Arizona Parkinson’s Disease Consortium. The Shacka Lab at the University of Alabama at Birmingham will process human brain tissue for biochemical analysis of alpha-Gal A protein levels and function (enzymatic activity). The Auray-Blais Lab at Universite de Sherbrooke (Quebec, Canada) will process brain tissue for analysis of lipid molecules that are ordinarily broken down by alpha-Gal A, and which are predicted to accumulate in Parkinson’s disease brain if alpha-Gal A levels or function are compromised.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
If alpha-Gal A is found to be decreased in Parkinson’s disease brain, this would suggest a novel drug target — with drugs that are already approved for clinical use — that could be used to increase alpha-Gal A levels in Parkinson’s disease patients as a potential means of delaying disease progression. This project also has the potential for identifying several new biomarkers for Parkinson’s disease that could help with future diagnosis and treatment of the disease.
Anticipated Outcome:
If their hypothesis is proven correct, the researchers will observe a decrease in alpha-Gal A levels and/or function in Parkinson’s disease brain, as well as a buildup of lipid molecules ordinarily broken down by alpha-Gal A. This would justify an immediate need for pre-clinical studies to determine if drugs that enhance alpha-Gal A levels in the brain can delay or prevent the progression of Parkinson’s disease-like pathology.