Our lab studies the pathogenesis of spinocerebellar ataxia type 1?a neurodegenerative disorder caused by a pathogenic polyglutamine expansion in the protein ataxin-1 (ATXN1). This supplemental application is inspired by novel links between ATXN1 and Alzheimer?s disease (AD) pathogenesis. Most notably, recent Genome Wide Association Studies (GWAS) have identified variants in the ATXN1 gene that influence AD risk; moreover, ATXN1 protein?both wild type and expanded?modulate the levels of beta-secretase 1 (BACE1), a key protease involved in the cleavage of Amyloid Protein Precursor (APP) that results in the production of the amyloidogenic peptide A beta. The overarching hypothesis of this application, therefore, is that there are common pathways in these two otherwise disparate proteinopathies. We envisage that our experiments testing this hypothesis will lead to novel insights particularly in combating cognitive decline in both these syndromes.
NIH ExPorter
NIH ExPorter