Superoxide Dismutase 1 in Health and Disease: How a Frontline Antioxidant Becomes Neurotoxic. Issue 17 (19th November 2020)

• Record Type: Journal Article
• Authors: Trist, Benjamin G.; Hilton, James B.; Hare, Dominic J.; Crouch, Peter J.; Double, Kay L.
• Is Part Of: Angewandte Chemie international edition. Volume 60:Issue 17(2021)
• Page Start: 9215
• Page End: 9246
• Publication Date: 2020-11-19
• Subjects: antioxidants -- copper -- Cu/Zn superoxide dismutase -- neurodegeneration -- protein misfolding; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202000451
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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. Abstract : This review summarizes contemporary understanding of the biology of Cu/Zn superoxide dismutase 1 (SOD1) from SOD1 genetics through to protein function and stability. Our cumulative knowledge of these processes is advancing efforts to identify and target pathways of neurotoxicity driven by atypical SOD1 in multiple incurable neurodegenerative conditions.