Project Overview

In Canada, the annual cost to care for individuals with neurodegenerative diseases is over $10.4 billion. There are no therapeutic interventions that sufficiently prevent or treat neurodegenerative diseases because the cause of neurodegeneration is complex and not well understood. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by the dysfunction and death of neurons in the brain and spinal cord responsible for voluntary movement. Neurons important for cognition and memory can also be affected in the disease. Recent studies have shown brain cells of individuals with neurodegenerative diseases, including ALS, accumulate small globules (droplets) of lipid (fat), indicating abnormal metabolism of fatty acids are involved in disease toxicity. Our research project aims to investigate how pathways of lipid metabolism are disrupted in ALS, using our mouse model of familial ALS due to mutations in the FUS gene. ALS-FUS mice have defects in both motor function and cognition. Importantly, we have observed aberrant accumulation of lipid droplets and toxic lipid by products in specific brain regions and neural cell-types (e.g., neurons and astrocytes) that correspond with impaired brain function. We will determine how FUS mutants affect fatty acid metabolism and promote disease toxicity, as well as test the more general involvement of fatty acid metabolism in promoting disease pathogenesis using models of other familial forms of ALS. The results will help us understand the importance of lipid dysregulation in ALS and point to potential new targets for intervention.

Principal Investigator

Chantelle Sephton , Université Laval

Team Members

Partners and Donors

ALS Society of Canada