Superoxide Dismutase 1 in Health and Disease: How a Frontline Antioxidant Becomes Neurotoxic

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.

Automated summary

Cu/Zn superoxide dismutase (SOD1) is a crucial antioxidant enzyme in eukaryotic life, with mitochondrial aerobic respiration increasing cellular superoxide production and reliance on SOD1. Diseases of the central nervous system often involve disruptions in SOD1 biology, revealing complex molecular characteristics that differentiate healthy from disease-contributing SOD1 proteins. This review highlights current knowledge of SOD1 biology, from genetics to protein function and stability.