Alpha-Galactosidase A and Glycosphingolipid Metabolites as Putative Biomarkers for Parkinsonís Disease
Access to Data and Biospecimens, 2013
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 Parkinsonís disease. This project will determine if alpha-Gal A is present at lower levels or has less function in Parkinsonís disease brain, and also if there is a buildup of lipids that are ordinarily degraded by alpha-Gal A.
Brains from control patients and from patients with three different ďstagesĒ of Parkinsonís disease grouped by increasing severity of their brain pathology will be obtained from the Arizona Parkinsonís 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 Parkinsonís disease brain if alpha-Gal A levels or function are compromised.
Relevance to Diagnosis/Treatment of Parkinsonís Disease: † † † † † † † † † ††
If alpha-Gal A is found to be decreased in Parkinsonís disease brain, this would suggest a novel drug target ó with drugs that are already approved for clinical use ó that could be used to increase alpha-Gal A levels in Parkinsonís disease patients as a potential means of delaying disease progression. This project also has the potential for identifying several new biomarkers for Parkinsonís 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 Parkinsonís 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 Parkinsonís disease-like pathology.
Assistant Professor at Universitť de Sherbrooke
Location: Sherbrooke, Quebec, Canada
Assistant Professor in the Department of Pathology, Molecular and Cellular Pathology Division at University of Alabama at Birmingham
Location: Birmingham, Alabama, United States