报告题目：Potential Therapeutic Strategies via Targeted Degradation of The Mutant HTT Protein

报告人：鲁伯埙 复旦大学

主持人：李大力 研究员

报告时间：2021年11月3日 14：00

报告地点：闵行校区生命科学学院534报告厅

报告人简介：

鲁伯埙，现任复旦大学特聘教授、博士生导师。先后获国家杰青、牛顿高级学者、教育部青年科学奖、科学探索奖、谈家桢创新奖等。博士毕业于美国宾夕法尼亚大学，其后在国际药企Novartis任总裁博士后。2012年底全职回国在复旦大学开展独立工作，致力于遗传性神经退行性疾病的致病机理和干预策略研究。揭示了疾病的源头机制和随时间加速恶化的机制、发现多个干预药靶、提出并实现了自噬小体绑定化合物（ATTEC）这一药物研发新概念。近年来作为通讯作者发表论文30余篇于Nature、Nature Neuroscience、Nature Chemical Biology等期刊，部分成果被领域同行于Nature等期刊十余次次撰写专文进行评述推荐。2019年作为最终通讯作者发表的Nature论文入选了Nature期刊评选的2019年度十大杰出论文（10 Remarkable Papers from 2019）。

报告内容：

Huntington’s disease (HD) is an autosomal dominant monogenetic disease mainly caused by the mutant huntingtin protein (mHTT) that contains an expanded polyglutamine (polyQ) tract, and lowering the level of mHTT may provide promising therapeutic strategies for HD. In this talk, I will present some of the published data from my group aiming at identifying different compounds that are capable of lowering mHTT as well as some preliminary data showing potential therapeutic benefits of these compounds in cellular and animal models. I will focus on our recent study demonstrating the possibility of targeting mHTT for autophagic degradation in an allele-selective manner by small molecule compounds based on the concept of autophagosome-tethering compounds (ATTEC). Due to the constraints from the biotech company that I co-founded, I am not allowed to talk about the unpublished progresses, but I will briefly discuss some of the directions that we are working on, including development of additional HD/polyQ-targeting compounds and the ATTEC strategy.