报告题目：Sigma 1 receptor as potential therapeutic target for neurodegenerative disorders
报告人：Ilya Bezprozvanny, Ph.D., D.Sci.
UT Southwestern Medical Center at Dallas,Dallas, Texas, USA
St Petersburg Polytechnical University, St Petersburg, Russia
报告地点：生物药学1号楼105会议室
报告时间：2019年11月13日10：00
邀请人：李卫东教授（liwd@sjtu.edu.cn）
报告人简介：
Ilya Bezprozvanny received M.Sci in Physics (1989) from the St Petersburg Polytechnical University and a Ph.D. in Cell Biology (1992) from the Institute of Cytology Russian Academy of Sciences (scientific advisors - Alex P. Naumov and Galina N. Mozhayeva). As a part of his training, Ilya worked with Barbara E. Ehrlich (1990-1994) at the University of Connecticut Health Center at Farmington, Connecticut and then with Richard W. Tsien (1994-1996) in the Department of Molecular and Cellular Physiology at Stanford University Medical Center, Stanford, California. In 1996, Ilya joined the faculty of UT Southwestern Medical Center as an Assistant Professor. Ilya is a Professor (2007) in the Department of Physiology and a member of the Neuroscience and Integrative Biology graduate programs.
For further information see: http://www4.utsouthwestern.edu/ilya/index.html
报告摘要/Abstract:
Sigma-1 receptor (S1R) is a multi-functional, ligand-operated protein situated in endoplasmic reticulum (ER) membranes and changes in its function and/or expression have been associated with various neurological disorders including amyotrophic lateral sclerosis/frontotemporal dementia, Alzheimer's (AD) and Huntington's diseases (HD). S1R agonists are broadly neuroprotective and this is achieved through a diversity of S1R-mediated signaling functions that are generally pro-survival and anti-apoptotic; yet, relatively little is known regarding the exact mechanisms of receptor functioning at the molecular level. This review summarizes therapeutically relevant mechanisms by which S1R modulates neurophysiology and implements neuroprotective functions in neurodegenerative diseases. These mechanisms are diverse due to the fact that S1R can bind to and modulate a large range of client proteins, including many ion channels in both ER and plasma membranes. We summarize the effect of S1R on its interaction partners and consider some of the cell type- and disease-specific aspects of these actions. Besides direct protein interactions in the endoplasmic reticulum, S1R is likely to function at the cellular/interorganellar level by altering the activity of several plasmalemmal ion channels through control of trafficking, which may help to reduce excitotoxicity. Moreover, S1R is situated in lipid rafts where it binds cholesterol and regulates lipid and protein trafficking and calcium flux at the mitochondrial-associated membrane (MAM) domain. This may have important implications for MAM stability and function in neurodegenerative diseases as well as cellular bioenergetics. We also summarize the structural and biochemical features of S1R proposed to underlie its activity. In conclusion, S1R is incredibly versatile in its ability to foster neuronal homeostasis in the context of several neurodegenerative disorders.
