当期文章

小分子化合物在神经元重编程中的应用研究进展

戴子为¹, 刘红¹, 袁一旻^1,2, 张静宜¹, 秦尚尧¹, 苏志达^1,*

¹海军军医大学基础医学院神经生物学教研室，分子神经生物学教育部重点实验室，上海 200433；²海军军医大学麻醉系疼痛治疗学研究室，上海 200433

摘要

神经元重编程是将非神经元成体细胞转分化为神经元的一项创新性技术，能够补充、替代丢失或受损的神经元，为中枢神经系统再生修复提供了一种潜在的有效策略。在细胞内高表达转录因子是诱导神经元重编程一种常用的重要手段，但其重编程效率比较低，且导入外源基因可能引起宿主基因组不稳定或诱发基因突变，从而限制了它们未来的临床转化应用。相对于转录因子，小分子化合物在神经元重编程领域具有得天独厚的优势，能够克服传统转录因子诱导神经元重编程的诸多局限性，具有更好的应用前景。本文就近年来小分子化合物介导的神经元重编程的相关研究进展及其在中枢神经系统再生修复中的应用进行简要综述。

关键词： 小分子化合物; 神经元重编程; 中枢神经系统; 神经再生修复

Advances in application of small-molecule compounds in neuronal reprogramming

DAI Zi-Wei¹, LIU Hong¹, YUAN Yi-Min^1,2, ZHANG Jing-Yi¹, QIN Shang-Yao¹, SU Zhi-Da^1,*

¹Department of Neurobiology, College of Basic Medicine, Key Laboratory of Molecular Neurobiology of Ministry of Education, Naval Medical University, Shanghai 200433, China；²Department of Pain Medicine, School of Anesthesiology, Naval Medical University, Shanghai 200433, China

Abstract

Neuronal reprogramming is an innovative technique for converting non-neuronal somatic cells into neurons that can be used to replace lost or damaged neurons, providing a potential effective therapeutic strategy for central nervous system (CNS) injuries or diseases. Transcription factors have been used to induce neuronal reprogramming, while their reprogramming efficiency is relatively low, and the introduction of exogenous genes may result in host gene instability or induce gene mutation. Therefore, their future clinical application may be hindered by these safety concerns. Compared with transcription factors, small-molecule compounds have unique advantages in the field of neuronal reprogramming, which can overcome many limitations of traditional transcription factor-induced neuronal reprogramming. Here, we review the recent progress in the research of small-molecule compound-mediated neuronal reprogramming and its application in CNS regeneration and repair.

Key words: small-molecule compounds; neuronal reprogramming; central nervous system; neural regeneration and repair

收稿日期：　　录用日期：

通讯作者：苏志达　　E-mail:

DOI: 10.13294/j.aps.2025.0011

引用本文：

戴子为, 刘红, 袁一旻, 张静宜, 秦尚尧, 苏志达. 小分子化合物在神经元重编程中的应用研究进展[J]. 生理学报 2025; 77 (1): 181-193.

DAI Zi-Wei, LIU Hong, YUAN Yi-Min, ZHANG Jing-Yi, QIN Shang-Yao, SU Zhi-Da. Advances in application of small-molecule compounds in neuronal reprogramming. Acta Physiol Sin 2025; 77 (1): 181-193 (in Chinese with English abstract).