题 目：Understanding neuronal cell biology during development and maintenance of the nervous system

主 讲：沈康 教授

时 间：2024年12月2日（周一）下午16:20-17:30

地 点：琳恩图书馆111报告厅

报告摘要：

Neurons are long-lived, terminally differentiated cells with limited regenerative capacity. Cellular stressors such as endoplasmic reticulum (ER) protein folding stress and membrane trafficking stress accumulate as neurons age and accompany agedependent neurodegeneration. Current strategies to improve neuronal resilience are focused on using factors to reprogram neurons or targeting specific proteostasis pathways. We discovered a different approach. In an unbiased screen for modifiers of neuronal membrane trafficking defects, we unexpectedly identified a role for histone deacetylases (HDACs) in limiting cellular flexibility in choosing cellular pathways to respond to diverse types of stress. We show that genetic or pharmacological inactivation of HDACs results in improved neuronal health in response to ER protein folding stress and endosomal membrane trafficking stress in C. elegans and mammalian neurons. Surprisingly, HDAC inhibition enabled neurons to activate latent proteostasis pathways tailored to the nature of the individual stress, instead of generalized transcriptional upregulation. These findings shape our understanding of neuronal stress responses and suggest new therapeutic strategies to enhance neuronal resilience.

嘉宾简介：

沈康博士，美国斯坦福大学生物系和病理学系终身教授，吴蔡神经科学研究所所长，霍华德休斯医学研究所研究员（2008年 – 至今）。主要致力于研究动物发育过程中神经环路形成的分子机制。研究成果以通讯作者或第一作者身份发表在Cell、 Science、Nature、 Neuron和Nat Neurosci等顶级学术期刊上。其系统和深入的研究工作为理解突触发育、轴突运输和树突发育等生命过程中的分子机制做出了非常重要的贡献。获得Alfred Sloan award和Searle Scholar award等多种荣誉。长期担任Nature、 Neuron、Dev Cell、 eLIFE和PNAS等学术期刊的审稿人。