Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, is an inherited neurodegenerative disorder that is caused by a mutation in ataxin-3. At present, effective treatment is not available for this disease, and the key mechanisms that underlie neuronal dysfunction are unknown. Ataxin-3 is present in many tissues, including non-neuronal cell types, where it functions in the cellular machinery controlling protein abundance, folding, and transport (protein homeostasis, or proteostasis). Maintenance of protein homeostasis is essential, as imbalances in any of these processes can have deleterious consequences on cell function and organismal health. We are planning to study protein homeostasis in neuronal and non-neuronal tissues in the nematode worm C. elegans, which has been genetically engineered to have SCA3. Detailed knowledge of cell type-specific events and regulation across tissues will not only help to better understand the disease mechanism, but may also lead to new therapeutic approaches for SCA3 and potentially other neurodegenerative diseases.
|Effective start/end date||1/1/17 → 12/31/17|
- National Ataxia Foundation (Letter 12/16/2016)