Grant: Joint Canada-Israel Health Research Program

The World Health Organization recently stated that the burden of mental and neurological disorders, which are highly prevalent worldwide, has been seriously underestimated by traditional epidemiological methods, which are biased towards mortality and disregard disability rates. Neurodegenerative diseases are predicted to surpass cancer as the second leading cause of death in Canada by 2040. Learning, memory and perception rely on an intricate network of proteins that orchestrate higher cognitive functions of the human brain. An important biological process regulating the function of these molecules is protein synthesis, also termed translation. Dysregulation of translation leads to pathological conditions such as Alzheimer's disease (AD), Parkinson's disease, Motor Neuron disease, Huntington's disease and prion diseases. A key molecule regulating protein synthesis is eIF2. Recent studies have shown that modulation of eIF2 activity can be utilized to enhance learning and memory in mice. We will use advanced genetic mouse models of eIF2, combined with gene discovery studies to identify the molecular mechanisms by which eIF2 regulates cognition. Knowledge gained from this project has the potential to direct treatment strategies targeting the eIF2 in patients with memory deficits to alleviate the cognitive and neurological symptoms associated with AD. Promoting our understanding of eIF2 control should have a significant impact on the design of prophylactic and post-diagnosis treatments for patients worldwide.