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SOD1 aggregation and ALS: role of metallation states and disulfide status.
Sheng, Yuewei; Chattopadhyay, Madhuri; Whitelegge, Julian; Valentine, Joan Selverstone.
Afiliación
  • Sheng Y; Department of Chemistry and Biochemistry, UCLA, Los Angeles, CA 90095, USA.
Curr Top Med Chem ; 12(22): 2560-72, 2012.
Article en En | MEDLINE | ID: mdl-23339308
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the death of motor neurons. About 10% of ALS cases are inherited (familial), and a large subset of them are caused by mutations in the gene encoding the copper-zinc superoxide dismutase (SOD1). The detection of SOD1-positive inclusions in familial ALS patients suggests the role of SOD1 aggregation underlying the pathology of familial ALS. Although SOD1 mutant proteins are different in structure, stability and activity, they all exhibit a higher aggregation propensity than wild-type SOD1. We here review the recent studies on the role of metallation states and disulfide status in the unfolding, misfolding, and aggregation of SOD1. Investigations of the mechanism of SOD1 aggregation enhance our understanding of onset and progression of ALS and have implications for therapeutic approaches for treating ALS.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Superóxido Dismutasa / Disulfuros / Esclerosis Amiotrófica Lateral Límite: Animals / Humans Idioma: En Revista: Curr Top Med Chem Asunto de la revista: QUIMICA Año: 2012 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Emiratos Árabes Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Superóxido Dismutasa / Disulfuros / Esclerosis Amiotrófica Lateral Límite: Animals / Humans Idioma: En Revista: Curr Top Med Chem Asunto de la revista: QUIMICA Año: 2012 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Emiratos Árabes Unidos