title: Copper Homeostasis as a Therapeutic Target in Amyotrophic Lateral Sclerosis with SOD1 Mutations.
abstract: Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease affecting both upper and lower motor neurons, and currently, there is no cure or effective treatment. Mutations in a gene encoding a ubiquitous antioxidant enzyme, Cu,Zn-superoxide dismutase (SOD1), have been first identified as a cause of familial forms of ALS. It is widely accepted that mutant SOD1 proteins cause the disease through a gain in toxicity but not through a loss of its physiological function. SOD1 is a major copper-binding protein and regulates copper homeostasis in the cell; therefore, a toxicity of mutant SOD1 could arise from the disruption of copper homeostasis. In this review, we will briefly review recent studies implying roles of copper homeostasis in the pathogenesis of SOD1-ALS and highlight the therapeutic interventions focusing on pharmacological as well as genetic regulations of copper homeostasis to modify the pathological process in SOD1-ALS.
authors.affiliation: Laboratory for Mechanistic Chemistry of Biomolecules, Department of Chemistry, Keio University, Yokohama 223-8522, Japan. tokuda@chem.keio.ac.jp.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Tokuda
authors.affiliation: Laboratory for Mechanistic Chemistry of Biomolecules, Department of Chemistry, Keio University, Yokohama 223-8522, Japan. furukawa@chem.keio.ac.jp.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Furukawa
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000818:Animals; D002614:Chelating Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D000072105:Superoxide Dismutase-1 / Q000235:genetics*
chemical_list: D002614:Chelating Agents; C000606290:SOD1 protein, human; D003300:Copper; D000072105:Superoxide Dismutase-1
keywords: Cu,Zn-superoxide dismutase; amyotrophic lateral sclerosis; copper homeostasis