Strategies to promote the maturation of ALS-associated SOD1 mutants: small molecules return to the fold

• Published in: Neural regeneration research Vol. 14; no. 9; pp. 1511 - 1512
• Main Authors: McAlary, Luke, Yerbury, Justin
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer India Pvt. Ltd 01.09.2019; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd; School of Chemistry and Molecular Bioscience, Molecular Horizons, Faculty of Science, Medicine and Health, University of Wollongong, NSW, Australia; Illawarra Health and Medical Research Institute, Wollongong, NSW, Australia; Wolters Kluwer - Medknow; Wolters Kluwer Medknow Publications
• Subjects: Amyotrophic lateral sclerosis; Care and treatment; Enzymes; Gene mutation; Genetic aspects; Medical schools; Mutation; Nervous system; Nervous system diseases; Neurons; Paralysis; Proteins; Superoxides; Telbivudine
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.255962

(Cu)IIATSM (CuATSM) promotes the proper folding of familial amyotrophic lateral sclerosis (fALS)-associated copper, zinc superoxide dismutase (SOD1): ALS is a progressive neurodegenerative disease that affects motor neurons in the cortex and spinal cord, resulting in paralysis and ultimately death. Recently, a copper (Cu)-based small molecule called CuATSM was found to be effective at treating multiple transgenic mouse models expressing human SOD1-fALS protein (Soon et al., 2011; Roberts et al., 2014). [...]the selenium-based antioxidant compound ebselen was shown to significantly increase the dimer-binding affinity of SOD1-fALS mutants in vitro and exert minimal toxicity to cultured cells (Capper et al., 2018). [...]ebselen may prove to be a useful lead compound in this class of drug, as in-cell nuclear magnetic resonance previously showed that cells expressing G93A or A4V SOD1 in the presence of ebselen were fully disulfide oxidized (Capper et al., 2018), whereas ~95% of the SOD1 expressed in the absence of ebselen existed in a disulfide reduced state.