Seminar: Presenilins in synaptic function and Alzheimer/'s disease

Title:  Presenilins in synaptic function and Alzheimer's disease

Speaker:  Jie Shen, PhD

                  Professor of Neurology

                  Harvard Medical School

                  Center for Neurologic Diseases

Time:  10:00-11:00, 7th Apr. 2015

Place:  Room B502, Research Building, School of Medicine

Host: Professor Shumin Duan

Introduction:

    The major research interests in the Shen's laboratory focus on elucidation of the pathogenic mechanisms of Alzheimer's and Parkinson's diseases. We employ a multidisciplinary approach based on the generation and analysis of mouse models, with the goal of understanding how pathogenic mutations perturb the normal in vivo function of gene products linked to these disorders. We discovered that the major Alzheimer's disease genes, presenilins, are essential for normal neuronal physiology and survival in the adult brain. Specifically, we found that presenilin inactivation causes striking age-dependent neurodegeneration that strongly resembles the neuropathology of Alzheimer's disease. Neuropathological changes in these mice are preceded by a decrease in presynaptic glutamate release and impairment in NMDA receptor function and synaptic plasticity, suggesting that synaptic dysfunction may trigger subsequent neurodegeneration. Based on these and other findings, we proposed the novel hypothesis that presenilin mutations cause Alzheimer's disease through a loss-of-function pathogenic mechanism.