神经退行性疾病是一类以广泛的神经元丢失或结构和功能性进行性变性为主要病理特征的疾病总称，给即将到来的老龄化社会造成极大的精神和医疗负担。促进神经元再生、恢复受损神经元数量和功能有望从根本上逆转疾病病程，但目前此类临床药物极其缺乏。促进线粒体生物合成及动力学平衡改善线粒体功能是一种重要的促神经元再生策略。申请人前期设计合成的神经保护剂T-006可促进帕金森病(PD)和脑中风(t-MCAO)大鼠脑区神经元再生，并促进线粒体生物合成，展现出独特的抗神经退行性疾病治疗潜力。但T-006是如何发挥促神经再生作用以及其具体的作用机理是什么还不明确。本项目将通过体内外研究PGC1α过表达和沉默后对T-006促线粒体生物合成、分裂/融合及神经再生的影响；并借助iTRAQ标记联合2D-LC-MS/MS定量蛋白质组学技术，阐明T-006改善线粒体功能促进神经元再生机制，为开发新型促神经再生药物提供理论基础。

Neurodegenerative diseases are a group of diseases that are characterized by extensive neuronal loss and progressive degeneration of structure and function as major pathological features, which causes a great mental and medical burden to the upcoming ageing society. If we can effectively promote the regeneration of neurons, restore the number and function of damaged neurons, it is expected to fundamentally reverse the disease course, but few drugs were used in clinic. Promoting mitochondrial biogenesis and dynamics can improve mitochondrial function, which is an effective strategy for stimulating neuronal regeneration. The neuroprotective agent T-006, which was designed and synthesized by the applicant, can induce the neurogenesis in Parkinson’s disease (PD) and transient middle cerebral artery occlusion (t-MCAO) rats and promote mitochondrial biogenesis, and show potential therapeutic effects in PD and stroke as well as the other neurodegenerative disorders. However, how T-006 exerts its role in promoting nerve regeneration and its exact mechanism has not been systematically revealed. Thus, this project will deep investigate the effects of overexpression and silencing of PGC1α on mitochondrial biosynthesis, division/fusion and nerve regeneration of T-006. Moreover, To elucidate the role of T-006 in improving mitochondrial function and promoting neuronal regeneration by using the quantitative proteomics technology with iTRAQ labeling in combination with 2D-LC-MS/MS method. We hope to promote the compound T-006 into clinical candidate drug and provide a theoretical basis for the development of new neurogenesis drugs through the above theoretical and experimental researches.