An attempt to treat amyotrophic lateral sclerosis by intracellular copper modification using ammonium tetrathiomolybdate and/or metallothionein: Fundamentals and perspective

Shin Ichi Ono, Ei Ichi Tokuda, Eriko Okawa, Shunsuke Watanabe

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

Mutation in superoxide diamutasel (SOD1) is a cause of hereditary form of amyotrophic lateral sclerosis (ALS). Novel acquired toxicity (gain-of-function) is believed to play a crucial role. We propose that the nature of mutant SOD1 toxicity is disruption of intracellular Cu homeostasis. We provide evidences that copper transporters and chaperons are geared to accumulate Cu ion in the cells, and its excretion is downregulated with mutant SOD1 ("intracellular copper dysregulation" theory). Intracellular Cu modification using a Cu chelator and/or metallothionein resulted in a favorable outcome in an experimental study with a rodent model for hereditary form of ALS.

Original languageEnglish
Title of host publicationBrain Diseases and Metalloproteins
PublisherPan Stanford Publishing Pte. Ltd.
Pages367-405
Number of pages39
ISBN (Print)9789814316019
DOIs
Publication statusPublished - 2012 Jul 31
Externally publishedYes

Fingerprint

Metallothionein
Amyotrophic Lateral Sclerosis
Toxicity
Copper
Chelating Agents
Superoxides
Rodentia
Homeostasis
Down-Regulation
Ions
Mutation
tetrathiomolybdate

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ono, S. I., Tokuda, E. I., Okawa, E., & Watanabe, S. (2012). An attempt to treat amyotrophic lateral sclerosis by intracellular copper modification using ammonium tetrathiomolybdate and/or metallothionein: Fundamentals and perspective. In Brain Diseases and Metalloproteins (pp. 367-405). Pan Stanford Publishing Pte. Ltd.. https://doi.org/10.4032/9789814364072

An attempt to treat amyotrophic lateral sclerosis by intracellular copper modification using ammonium tetrathiomolybdate and/or metallothionein : Fundamentals and perspective. / Ono, Shin Ichi; Tokuda, Ei Ichi; Okawa, Eriko; Watanabe, Shunsuke.

Brain Diseases and Metalloproteins. Pan Stanford Publishing Pte. Ltd., 2012. p. 367-405.

Research output: Chapter in Book/Report/Conference proceedingChapter

Ono, Shin Ichi ; Tokuda, Ei Ichi ; Okawa, Eriko ; Watanabe, Shunsuke. / An attempt to treat amyotrophic lateral sclerosis by intracellular copper modification using ammonium tetrathiomolybdate and/or metallothionein : Fundamentals and perspective. Brain Diseases and Metalloproteins. Pan Stanford Publishing Pte. Ltd., 2012. pp. 367-405
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