Identification of cell-type-specific dysregulated mRNA translation in Alzheimer's disease
Dr. Vijendra Sharma
University of Windsor
FUNDER: Equally Science, Vice-President Research & Innovation (VPRI)
Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by a gradual loss of memory and cognition. The integrated stress response (ISR) pathway is an evolutionarily conserved pathway that gets triggered in AD. Prolonged cellualar stress and ISR activation in the brains of AD patients inhibit general protein synthesis and impair long-term memory (LTM) formation. Although there is substantial progress in understanding the causal link between ISR activity and memory consolidation, the ISR-downstream molecular mechanisms causing memory loss and the cell types mediating the effect on AD pathology remain unresolved. By examining the dysregulation of mRNA translation in distinct cell types, the cell types that preferentially promote neurotoxicity in AD can be identified.
By expanding the expertise in AD and ISR, further understanding of the underlying mechanisms that lead to the impairment of LTM formation in AD patients can be discovered. Ultimately, the normalization of translation in susceptible cell type(s) may offer a novel appraoch to treating AD.