基于金属的神经退行性疾病治疗策略*

本文综述了金属离子在神经退行性疾病中的重要作用以及针对该类疾病金属治疗药物的研究进展。以老年痴呆症和帕金森氏症为代表，结合本课题组的初步研究结果，讨论了金属离子在蛋白质聚集与氧化应激反应中的重要作用，暗示金属螯合策略应成为治疗该类疾病的首选策略，并介绍了数种已用于或即将用于临床实验的金属螯合制剂；还介绍了烷基化神经退行性疾病相关蛋白的金属结合位点，可以显著抑制该蛋白质聚集体的形成和活性氧的产生，这可能是继螯合策略后一种更有发展潜力的神经退行性疾病治疗方法。

Metal-Based Therapeutic Strategies of Neurodegenerative Diseases

The role of metal ions in both the pathology of neurodegenerative diseases and their treatments are summarized. The metal ion-mediated protein aggregation and oxidative stress in such as Alzheimer’s and Parkinson’s are discussed by integrating our preliminary data. The progress obtained to date shows that the metal chelation might be a preferred strategy in treatments of neurodegenerative diseases. Thus, a number of metal-chelating agents have been introduced into clinical trials. The alkylation of metal binding sites in the disease-linked proteins can significantly inhibit the formation of protein aggregates and reactive oxygen species, suggesting that this strategy may be a potential method to treat the diseases. Contents
1 Introduction
2 Brain metal ions and maintenance of their homeostasis
3 Metal ion-induced protein aggregation and oxidative stress
4 Protein aggregation and oxidative stress in Alzheimer's disease
5 Oxidative stress and α-synuclein aggregation in Parkinson's disease
6 Other neurodegenerative diseases
7 Therapeutic strategies
8 Conclusions