讲座题目:Novel aspects of GDNF biology

主讲人: Mart Saarma 教授

主持人:袁崇刚 教授

开始时间:2014-06-23 10:30

讲座地址:闵行校区bevictor伟德官网534报告厅

主办单位:bevictor伟德官网 科技处

 

报告人简介：

Mart Saarma is the Professor of Biotechnology and Director of the Laboratory of Molecular Neuroscience at the Institute of Biotechnology, University of Helsinki, Finland. He has studied the structure,biology and therapeutic potential neurotrophic factors and their receptors. His recent studies are focused on the role of neurotrophic factors in development and neurodegenerative diseases. His group has characterized several new GDNF family receptors and demonstrated that RET receptor tyrosine kinase is the signaling receptor for GDNF. Recently his group has discovered a new neurotrophic factor CDNF and shown that it very efficiently protects and repairs dopamine neurons in vivo in animal models of Parkinson’s disease. He has received several domestic and international science prizes, including the Nordic Science Prize by Lundbeck Foundation in 2009.He is the member of several academies and EMBO.Currently he is the member of EMBO Council and of the Scientific Council of the European Research Council.

 

报告内容摘要：

In neurodegenerative diseases, including Parkinson’s disease (PD)neurons degenerate and die. Unfortunately all current therapies are unable to slow down or stop neurodegeneration in PD. Glial cell line-derived neurotrophic factor GDNF and its homologous protein neurturin are able to protect and also repair DA neurons in various animal models of PD, but the results of their Phase 2 clinical trials with Parkinson’s patients have given modest results. One of the reasons of this is our poor knowledge about the biology of GDNF especially in aging nervous system. We found that GDNF expression is negatively regulated via its 3’UTR in vitro and in vivo. Our data suggest suppression via direct interaction between Gdnf 3’UTR and miR-96 and miR-146a and identify other candidate miR-s for GDNF regulation. Further, we show that elevation of endogenous GDNF by 3’UTR replacement in mice augments striatal extracellular dopamine (DA) clearance rate in DA concentration dependent manner, increases striatal DA levels and elevates the number of DA neurons in adult substantia nigra. Our results reveal post-natal functions of endogenous GDNF and highlight 3’UTR replacement as a potent genetic tool to study mammalian genes in vivo.