Grant: Operating Grant

Alzheimer's disease is a neurodegenerative disorder that attacks parts of the brain involved with learning and memory. The overarching goal of the research proposed in this application is to uncover mechanisms that could be targeted for the development of therapeutic agents capable of preventing neuronal death in Alzheimer's disease. The associated neurodegeneration is known to correlate with the accumulation of cellular stressors. How this contributes to disease is not understood. Recent evidence suggests that cell stress may progressively interfere with the function of the endoplasmic reticulum, an intracellular organelle that plays a vital role in a variety of cellular functions. Our preliminary findings suggest that as endoplasmic reticulum function deteriorates it provokes increased activation of a family of plasma membrane channels called pannexins, previously shown to be involved in cell death. Understanding how the endoplasmic reticulum regulates pannexin channel activity will provide novel insight leading to the rational design of innovative drugs of benefit in the treatment of Alzheimer's disease, and potentially other neurodegenerative disorders.