小分子化合物影响神经干细胞再生的思考

Thinking of Influences of Small Molecules on Neural Stem Cell Neurogenesis

近年来有不少研究兴趣聚焦于基于神经干细胞治疗阿尔茨海默病(Alzheimer’s disease,AD)等神经退行性疾病的策略。到目前为止,所谓的再生医学主要集中于用多能胚胎干细胞进行细胞移植治疗。虽然已经有了一些令人激动的研究结果,但胚胎干细胞替代治疗仍然面临一些障碍,包括免疫排斥、突变带来的过度生长、伦理学争论等。代之而起的探索是用小分子化合物直接调制内源性干细胞的命运,已经取得一些结果,但许多涉及神经干细胞与局部小环境的相互作用及神经干细胞特异性信号机制的基础问题有待阐明。对这些问题的研究可能深化对神经干细胞生物学的认识,并促进创新性治疗药物的问世。

Recently,there is considerable interest in the development of stem cellbased strategies for the treatment of Alzheimer's disease,one of the neurodegenerative diseases.To date,so-called regenerative approaches have focused mainly on the development of cell transplantation therapies using cells derived from pluripotent embryonic stem cells(ESCs).Although some exciting preliminary reports have been described in regard of the efficacy of ESC-derived replacement therapies,explorations involving ex vivo manipulated ESCs are hindered by events of mutation,immune rejection,and ethical controversy.An alternative approach involves direct in vivo modulation of endogenous adult stem cell populations using small molecules.Although many results have been reported,the interaction between neural stem cell and local niche and the specific signal mechanisms of neural stem cell remain to be elucidated.Here we present the thinking of the chemical approaches to the regulation of neural stem cell biology that are yielding new biological insights and that may potentially lead to innovative new drugs.