Copper homeostasis as a therapeutic target in amyotrophic lateral sclerosis with SOD1 mutations

Eiichi Tokuda, Yoshiaki Furukawa

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number636
JournalInternational Journal of Molecular Sciences
Volume17
Issue number5
DOIs
Publication statusPublished - 2016 May 1

Fingerprint

homeostasis
Amyotrophic Lateral Sclerosis
mutations
Copper
Homeostasis
copper
Mutation
Toxicity
toxicity
Neurodegenerative diseases
Gene encoding
Motor Neurons
proteins
Pathologic Processes
Mutant Proteins
Therapeutics
pathogenesis
Neurodegenerative Diseases
inorganic peroxides
causes

Keywords

  • Amyotrophic lateral sclerosis
  • Copper homeostasis
  • Cu, Zn-superoxide dismutase

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Inorganic Chemistry
  • Catalysis
  • Molecular Biology
  • Computer Science Applications

Cite this

Copper homeostasis as a therapeutic target in amyotrophic lateral sclerosis with SOD1 mutations. / Tokuda, Eiichi; Furukawa, Yoshiaki.

In: International Journal of Molecular Sciences, Vol. 17, No. 5, 636, 01.05.2016.

Research output: Contribution to journalArticle

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