Brain and Mind Centre and Discipline of Pharmacology, The University of Sydney, Camperdown, Sydney, New South Wales, 2050, Australia.
Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Victoria, 3052, Australia.
Angew Chem Int Ed Engl. 2021 Apr 19;60(17):9215-9246. doi: 10.1002/anie.202000451. Epub 2020 Nov 19.
Cu/Zn superoxide dismutase (SOD1) is a frontline antioxidant enzyme catalysing superoxide breakdown and is important for most forms of eukaryotic life. The evolution of aerobic respiration by mitochondria increased cellular production of superoxide, resulting in an increased reliance upon SOD1. Consistent with the importance of SOD1 for cellular health, many human diseases of the central nervous system involve perturbations in SOD1 biology. But far from providing a simple demonstration of how disease arises from SOD1 loss-of-function, attempts to elucidate pathways by which atypical SOD1 biology leads to neurodegeneration have revealed unexpectedly complex molecular characteristics delineating healthy, functional SOD1 protein from that which likely contributes to central nervous system disease. This review summarises current understanding of SOD1 biology from SOD1 genetics through to protein function and stability.
铜/锌超氧化物歧化酶（SOD1）是一种前沿的抗氧化酶，可催化超氧化物的分解，对大多数真核生物形式都很重要。线粒体有氧呼吸的进化增加了细胞中超氧化物的产生，从而增加了对 SOD1 的依赖。与 SOD1 对细胞健康的重要性一致，许多涉及中枢神经系统的人类疾病都涉及 SOD1 生物学的改变。但是，远非简单地展示 SOD1 功能丧失如何导致疾病，阐明异常 SOD1 生物学导致神经退行性变的途径的尝试揭示了出人意料的复杂分子特征，这些特征将健康、功能正常的 SOD1 蛋白与可能导致中枢神经系统疾病的 SOD1 蛋白区分开来。本综述总结了 SOD1 生物学的最新认识，从 SOD1 遗传学到蛋白质功能和稳定性。
