Définir des mécanismes dans la pathogenèse des maladies neurodégénératives afin de développer de nouvelles approches thérapeutiques qui ralentiront ou arrêteront la progression de la maladie

 

Rona Graham

Université de Sherbrooke

 

Domaine : vieillissement

Programme Chercheurs-boursiers - Junior 2

Concours 2019-2020

Currently, there are no effective therapies for Alzheimer disease (AD) or Huntington disease (HD) and therapeutic development efforts are hampered by the lack of affordable, expeditive and reliable markers to predict (AD) and/or monitor disease progression. Deficits in the sense of smell are a hallmark in several neurological disorders. These deficits occur early in the disease and correlate with global cognitive performance, depression and degeneration of olfactory regions in the brain. This evidence suggests that level of smell capability may be a potential marker of the disease and useful as an endpoint in clinical or animal therapeutic trials.

Using clinical, preclinical and molecular strategies, the overall goal of this research program is to dissect out the nature of the olfactory system dysfunction in order to define novel therapeutic approaches for AD and HD. Importantly this study will identify early endpoints and highlight the hazards associated with olfactory dysfunction (unaware of gas leaks, smoke). This work will also determine whether olfactory training results in rescue of the olfactory dysfunction and importantly, cognitive deficits. Identification of markers for AD and HD will contribute substantially to our understanding of the pathogenesis of the disease and brain-behaviour relationships, and enable assessment of the efficacy of putative therapies.

We are also doing basic research. Apoptosis, the process of a genetically programmed form of cell death that utilizes certain proteins called caspases, leads to the elimination of a cell without damaging other cells in the vicinity. In an average human adult, ~50 billion cells die by this process/day. Research indicates activation of caspase-6, a type of molecular scissors, occurs early in the programmed cell death pathway. We are investigating what proteins regulate caspase-6 to understand how it becomes activated. Exploring the biology of caspase-6 will provide valuable insights into fundamental biological mechanisms underlying cell death.