Superoxide Dismutase 1

[Petr75]

2020 Mar 6
The University of Sydney, Brain and Mind Centre, 94-100 Mallet Street, Camperdown, Sydney
Superoxide Dismutase 1 in Health and Disease: How a Front-Line Antioxidant Becomes Neurotoxic
https://pubmed.ncbi.nlm.nih.gov/3214483 ... eurotoxic/

Abstract

Cu/Zn superoxide dismutase (SOD1) is a front-line 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, with the clearest demonstration provided by cases of amyotrophic lateral sclerosis associated with SOD1 gene mutations. 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 contemporary understanding of SOD1 biology 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 mutant and wild-type SOD1 in multiple incurable neurodegenerative conditions.