One of the hallmark features of ARSACS is dysfunction and eventual death of Purkinje cells in the cerebellum, which contributes to ataxia. Strikingly, not all Purkinje cells become ill and die: rather, specific patterns of vulnerability and resilience to cell death are observed in both human patients and mouse models of ARSACs. Our work focuses on identification of the factors that promote resilience or prevent vulnerability to cell death. For example, we recently reported that both the location and molecular profile of Purkinje cells are involved in determining cell survival or death (Toscano-Marquez et al., 2021). We continue this line of research with a focus on three hypotheses: (1) Can improving mitochondria function prevent cell death and reduce ataxia progression? (2) Does a pH regulator act as a therapeutic agent for ARSACs treatment? (3) Do changes in non-neuronal cells impact cerebellar function in ARSACS? Finally, we continue to explore novel pathways that could be targeted for future therapeutics.
Grant: $191,000
Duration: second year of a 2 year project
Contact:
Dr. Alanna Watt, Department of Biology
McGill University, Bellini Life Science Building, room 265
3469 Sir William Osler, Montreal, Quebec Canada H3G 0B1
alanna.watt@mcgill.ca
Dr. Anne McKinney, Department of Pharmacology and Therapeutics
McGill University Bellini Life Science Building, room 167
3469 Sir William Osler, Montreal, Quebec Canada H3G 0B1
anne.mckinney@mcgill.ca