小分子蛋白聚集抑制剂研究进展.docVIP

神经退行性疾病治疗策略--小分子蛋白聚集抑制剂 刘庆彬* 刘博 李立斌 张福军 (河北师范大学化学与生物制药实验室，石家庄 050012) 摘 要 神经退行性疾病包括阿尔茨海默病(AD)、帕金森综合症（PD）、亨廷顿舞蹈症（HD） 肌肉萎缩性侧索硬化症(ALS)等已成为严重危害人类健康的重大疾病。已经被认识到有共同的细胞和分子机理；即某些基因发生突变，产生突变蛋白质，发生错误折叠，错误折叠蛋白导致蛋白聚集、纤维化产生细胞毒性，导致疾病发生。因此抑制蛋白聚集防止纤维化的发生成为治疗神经退行性疾病新的途径。本论文综述了近些年来神经退行性疾病发病机理、小分子蛋白聚集抑制剂研究进展，并对今后的研究进行了展望。 关键词：神经退行性疾病 错误折叠 蛋白聚集 小分子抑制剂 中图分类号: O621，Q51，TQ46 Small Molecule Inhibitors of Protein Aggregation as Therapeutic Strategies for Neurodegenerative Diseases Liu Qingbin* Liu Bo Li Libin Zhang Fhinaujun (Chemical Biopharmceutical Lab of Hebei Normal University , Shijiazhuang 050021, China) Abstract Neurodegenerative Diseases （e.g. Alzheimer’s disease(AD), Parkinson’s disease (PD) , Huntington’s disease(HD) and Amyotrophic lateral sclerosis (ALS)） have been the serious diseases harmful to human health.The common cell and molecular mechanism.of these diseases are characterised by gene mutation to form protein misfolding , aggregation, oligomers, protofibrils and fibrils which is toxic to neuron. Therefore, Inhibitting to protein aggregation and fibrils is a new therapeutic strategy for neurodegenerative diseases. In this article, the development of mechanism.of these diseases,and small molecule inhibitors of protein aggregation in recently years was reviewed and Finally the developing prospect was outlooked. Key words: neurodegenerative diseases; misfolding; protein aggregation; small molecule inhibitors 通讯联系人：e-mail：liuqingb@ Contents 1. Introduction 2.?- Amyloid peptide aggregation Inhibitors 3. Tau aggregation inhibitors 4. ?-Synuclein aggregation Inhibitors 5. Superoxide dismutase1 and huntingtin aggregation Inhibitors 6. Summary and outlook 1 引言 神经退行性疾病是一类由于神经元细胞发生渐进性功能异常及死亡，进而导致病人行为异常和功能障碍，引起过早死亡的神经性疾病。神经退行性疾病包括阿尔茨海默病(Alzheimer’s disease，AD)、帕金森综合症（Parkinson’s disease PD）、亨廷顿舞蹈症（Huntington’s disease） 肌肉萎缩性侧索硬化症(Amyotrophic lateral sclerosis ALS)等；神经退行性疾病的发生与年龄密切相关，随着世界人口平均寿命的逐年增加，人口老龄化日趋严重，神经退行性疾病的患者越来越多，已成为严重危害人类健康的重大疾病，目前神经退行性疾病已成为神经生物学、药理学、药物