Project 171361

As we live longer than ever before the World Health Organization predicts that neurodegenerative diseases like Amyotrophic Lateral Sclerosis, Alzheimer's, Huntington's and Parkinson's diseases will surpass cancer as the second leading cause of death in Canada by 2040. I am interested in finding neuronal survival mechanisms that reduce or prevent age-related nervous system decline from disease-associated proteins. Aging may be the unifying risk factor in nearly all neurodegenerative diseases. The discovery that single gene mutations can dramatically increase cell survival and delay aging in simple animals revealed that longevity has a genetic component. I hypothesize that these longevity genes may modify disease progression in humans, and that these genes may be new drug targets. The path from genetic mutation to neuronal decline is complex and takes decades in humans. By using simple models that recapitulate aspects of human disease it is possible to address my hypothesis. I have pioneered the use of the worm Caenorhabditis elegans to model neurodegeneration. I propose to establish new models and use them to explore the genetic pathways that protect against age-related neurodegeneration. The expected results are advances in understanding the relationships between longevity and cell survival pathways, which may reveal pharmaceutical targets or markers of disease progression. Finally, this work may uncover cell survival mechanisms applicable to other neurodegenerative diseases.

using C. elegans to model neurodegeneration and explore the genetic pathways that protect against age-related neurodegeneration