caa a22 4500 605543836 CHVBK 20210128100928.0 cr unu---uuuuu 210128e20150501xx s 000 0 eng 10.1007/s00109-015-1273-3 doi (NATIONALLICENCE)springer-10.1007/s00109-015-1273-3 Metal-deficient SOD1 in amyotrophic lateral sclerosis [Elektronische Daten] [James Hilton, Anthony White, Peter Crouch] Mutations to the ubiquitous antioxidant enzyme Cu/Zn superoxide dismutase (SOD1) were the first established genetic cause of the fatal, adult-onset neurodegenerative disease amyotrophic lateral sclerosis (ALS). It is widely accepted that these mutations do not cause ALS via a loss of antioxidant function, but elucidating the alternate toxic gain of function has proven to be elusive. Under physiological conditions, SOD1 binds one copper ion and one zinc ion per monomer to form a highly stable and functional homodimer, but there is now ample evidence to indicate aberrant persistence of SOD1 in an intermediate metal-deficient state may contribute to the protein's involvement in ALS. This review briefly discusses some of the data to support a role for metal-deficient SOD1 in the development of ALS and some of the outcomes from drug development studies that have aimed tomodify the symptoms of ALS by targeting the metal state of SOD1. The implications for the metal state of SOD1 in cases of sporadic ALS that do not involve mutant SOD1 are also discussed. The Author(s), 2015 Amyotrophic lateral sclerosis (ALS) nationallicence Motor neuron disease (MND) nationallicence Copper (Cu) nationallicence Zinc (Zn) nationallicence Cu/Zn superoxide dismutase (SOD1) nationallicence Protein misfolding nationallicence Diacetylbis(4-methylthiosemicarbazonato)copperII nationallicence Hilton James Department of Pathology, The University of Melbourne, 3010, Melbourne, Victoria, Australia aut White Anthony Department of Pathology, The University of Melbourne, 3010, Melbourne, Victoria, Australia aut Crouch Peter Department of Pathology, The University of Melbourne, 3010, Melbourne, Victoria, Australia aut Journal of Molecular Medicine Springer Berlin Heidelberg 93/5(2015-05-01), 481-487 0946-2716 93:5<481 2015 93 109 https://doi.org/10.1007/s00109-015-1273-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00109-015-1273-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hilton James Department of Pathology, The University of Melbourne, 3010, Melbourne, Victoria, Australia aut NATIONALLICENCE 700 1- White Anthony Department of Pathology, The University of Melbourne, 3010, Melbourne, Victoria, Australia aut NATIONALLICENCE 700 1- Crouch Peter Department of Pathology, The University of Melbourne, 3010, Melbourne, Victoria, Australia aut NATIONALLICENCE 773 0- Journal of Molecular Medicine Springer Berlin Heidelberg 93/5(2015-05-01), 481-487 0946-2716 93:5<481 2015 93 109