Journal article
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
Angewandte Chemie International Edition | WILEY-V C H VERLAG GMBH | Published : 2020
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 delineati..
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Awarded by National Health and Medical Research Council of Australia Program Grant
Awarded by Dementia Research Team Grant
Awarded by CogSleep Centre of Research Excellence
Awarded by National Health and Medical Research Council of Australia
Funding Acknowledgements
This study was supported by ForeFront, a large collaborative research group dedicated to the study of neurodegenerative diseases and funded by the National Health and Medical Research Council of Australia Program Grant (1132524), Dementia Research Team Grant (1095127) and CogSleep Centre of Research Excellence (1152945). B.G.T., D.J.H. and K.L.D. are funded by the National Health and Medical Research Council of Australia (1181864), Parkinson's NSW (Australia), the University of Sydney (Biomedical Science), The Motor Neurone Disease Research Institute of Australia and The Michael J. Fox Foundation for Parkinson's Research in partnership with the Shake It Up Australia Foundation. D.J.H. is funded by the National Health and Medical Research Council of Australia (1122981) in partnership with Agilent Technologies, who provide materials and research support. P.J.C. is funded by the University of Melbourne, the Motor Neurone Disease Research Institute of Australia (Jenny Barr Smith MND Research Grant), and FightMND. J.B.H. is funded by the Motor Neurone Disease Research Institute of Australia (Beryl Bayley Postdoctoral Research Fellowship). SOD1 Crystal structures were created using The PyMOL Molecular Graphics System, Version 2.0 Schrodinger, LLC (RCSB PDBs 1HL5, 2RSQ, 3ECU, 6FOL, 6FP6).