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

Benjamin G. Trist, James B. Hilton, Dominic J. Hare, Peter J. Crouch, Kay L. Double

Research output: Contribution to journalReview ArticleResearchpeer-review

77 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)9215-9246
Number of pages32
JournalAngewandte Chemie - International Edition
Volume60
Issue number17
DOIs
Publication statusPublished - 19 Apr 2021

Keywords

  • antioxidants
  • copper
  • Cu/Zn superoxide dismutase
  • neurodegeneration
  • protein misfolding

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