will take place on Tuesday, May 21, 2019 from 17:15 to 18:15 hours in CBBM Building, Ground Floor, Seminar Room B1/B2.
Host: Dr. Jan Wenzel
Institute of Experimental and Clinical Pharmacology and Toxicology
University of Lübeck
Abstract
In this talk I will give a brief introduction to the biology of G-protein coupled receptors and then proceed with our recent finding recently published in Glia.
Discovery of neuroprotective pathways is one of the major priorities for neuroscience. Astrocytes are the natural neuroprotectors and it is likely that brain resilience can be enhanced by mobilising their protective potential. Among G-protein coupled receptors expressed by astrocytes, two highly related receptors, GPR37L1 and GPR37, are of particular interest. Previous studies suggested that these receptors are activated by a peptide Saposin C and its neuroactive fragments (such as prosaptide TX14), which were demonstrated to be neuroprotective in various animal models by several groups. However, pairing of Saposin C or prosaptides with GPR37L1/GPR37 has been challenged and eventually GPR37L1/GPR37 regained their orphan status. We demonstrate that in their natural habitat, astrocytes, these receptors mediate a range of effects of TX14, including protection from oxidative stress. On the other hand, when recombinant GPR37L1 or GPR37 are expressed in HEK293 cells, they are not functional and do not respond to TX14, which explains unsuccessful attempts to confirm the ligand-receptor pairing. Therefore this study identifies GPR37L1/GPR37 as the receptors for TX14, and, by extension of Saposin C, and paves the way for the development of neuroprotective therapeutics acting via these receptors.
Biosketch
Prof. Kasparov received the MD degree with specialsation in therapeutics from the First Moscow Medical Institute in 1979 and completed the PhD degree from the same institute in 1982. After several years of research experience in Russisa and Germany (as Alexander von Humboldt Research Fellow), he completed a second doctoral degree in pharmacology at the Russian Academy of Medical Sciences in 1994. From 1994 to 1995 Prof. Kasparov was Visiting Research Fellow in Neurobiology at Harvard Medical School, USA. In the following years he was worked as Research Fellow, Lecturer and Reader in the Department of Physiology at the University of Bristol. Since 2009 he was appointed Professor of Molecular Biology in the School of Physiology, Pharmacology & Neuroscience at the University of Bristol.
