Nakamura Shinsuke, Shimazawa Masamitsu, Hara Hideaki
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University.
Biol Pharm Bull. 2018;41(7):1006-1013. doi: 10.1248/bpb.b17-00856.
Metallothioneins (MTs) are small-molecular weight metal-binding proteins involved in the maintenance of tissue structure, efficient metal metabolism, and metal detoxification and have an antioxidative effect. Moreover, MTs are expressed as four isoforms, and there are no known patterns in their localization with various effects. According to recent studies, MTs affect central nervous system (CNS) diseases, and many reports suggest that each isoform of MT has a protective effect against disease. Notably, MTs are involved in regions of diseases related to unmet medical needs, and MTs affect intractable neurological diseases, such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). This review specifically focuses on MT-related ocular diseases, cerebral ischemia, psychological disorders, ALS, and SMA. Each of these diseases has a separate cause, but the conditions are related to MTs. To understand the physiological roles of MTs in CNS diseases, we reviewed the current literature on the complex interactions between each MT, pathological conditions, and perspectives. We also discuss current evidence on the expression and function of MTs for diagnosis and new therapeutic strategies.
金属硫蛋白（MTs）是一种小分子重量的金属结合蛋白，参与组织结构的维持、有效的金属代谢和金属解毒，并具有抗氧化作用。此外，MTs以四种异构体形式表达，其定位尚无已知模式且具有多种效应。根据最近的研究，MTs会影响中枢神经系统（CNS）疾病，许多报告表明MT的每种异构体都对疾病具有保护作用。值得注意的是，MTs涉及与未满足的医疗需求相关的疾病区域，并且MTs会影响诸如肌萎缩侧索硬化症（ALS）和脊髓性肌萎缩症（SMA）等难治性神经疾病。本综述特别关注与MT相关的眼部疾病、脑缺血、心理障碍、ALS和SMA。这些疾病各自有独立的病因，但都与MTs有关。为了解MTs在中枢神经系统疾病中的生理作用，我们回顾了当前关于每种MT、病理状况及前景之间复杂相互作用的文献。我们还讨论了关于MTs表达和功能用于诊断及新治疗策略的当前证据。
