学术报告预告‖Brian MacVicar院士、Terrance P. Snutch院士、Yutian Wang院士深圳开讲

报告3

主题：Development of NMDAR Positive Allosteric Modulators as Novel Therapeutics for Brain Disorders

时间：2018年09月30日 16:00

地点：A504  会议室

主持：王立平  研究员

嘉宾：Yutian Wang , PhD

Professor of Djavad Mowafaghian Centre for Brain Health 

and Department of Medicine/Neurology, 

University of British Columbia, Vancouver, Canada

报告简介：

The N-methyl-D-aspartate subtype of glutamate receptor (NMDAR) is fundamental to many normal brain functions such as neurodevelopment, cognition and memory.  As such, its dysfunction contributes to the pathogenesis of many brain disorders/diseases ranging from acute and chronic neurodegeneration to mental illnesses.  Native NMDARs are tetrameric complexes comprised of GNR1 subunits with at least one type of GluN2 subunit.  Depending on the GluN2 subunits, NMDARs may have distinct functions.  Synaptic, predominantly GluN2A-containing, receptors are thought to be responsible for promoting the induction of long-term potentiation and neuronal survival.  In contrast, extra-synaptic, predominantly GluN2B-containing, receptors appear to promote the induction of long-term depression and neuronal death.  Using computer-based receptor modeling, chemical library screening, and functional characterizations, we have recently developed a class of GluN2A-NMDAR positive allosteric potentiators (Npams) and demonstrated their roles in activating pro-survival signaling and reducing excitotoxic/ischemic neuronal injuries in vitro and in vivo.  Our results not only validate GluN2A-specific roles of NMDARs in promoting cell survival, but also lead to the development of a new class of NMDAR-based neuroprotective modulators in stroke.