Grant: Operating Grant

Neurodegenerative diseases represent one of the leading causes of disability in the Canadian population. These conditions produce a range of symptoms and functional limitations that pose daily challenges to individuals and their families. Because the incidence of neurodegeneration increases with age, the burden of treating and living with neurodegenerative diseases may magnify as Canada's population ages. This proposal focuses on two genes, PRNP and ATXN1 directly involved in two neurodegenerative disorders, prion diseases (or transmissible spongiform encephalopathies), and spinocerebellar ataxia type 1 (or SCA1). Indeed, my laboratory recently discovered that these genes are dual-coding genes and produce two different proteins. PRNP produces the well-known prion protein (PrP) and alternative prion protein (AltPrP), and ATXN1 produces ataxin 1 (or ATXN1) and alternative ataxin 1 (AltATXN1). We will undertake the functional characterization of AltPrP and AltATXN1, and determine their impact on the functional regulation of their cognate proteins, PrP and ATXN1. Results are expected to shed light on how these two degenerative brain disorders develop and will indicate the potential of alternative-protein as novel therapeutic targets.