A Pathological Link Between Dysregulated Copper Binding in Cu/Zn-superoxide Dismutase and Amyotrophic Lateral Sclerosis

Overview

Journal J Clin Biochem Nutr

Specialty Biochemistry

Date 2022 Oct 10

PMID 36213785

Authors

Yoshiaki Furukawa

Affiliations

Soon will be listed here.

Abstract

Mutations in the gene coding Cu/Zn-superoxide dismutase (SOD1) are linked to a familial form of amyotrophic lateral sclerosis (ALS), and its pathological hallmark includes abnormal accumulation of mutant SOD1 proteins in spinal motorneurons. Mutant SOD1 proteins are considered to be susceptible to misfolding, resulting in the accumulation as oligomers/aggregates. While it remains obscure how and why SOD1 becomes misfolded under pathological conditions , the failure to bind a copper and zinc ion in SOD1 leads to the significant destabilization of its natively folded structure. Therefore, genetic and pharmacological attempts to promote the metal binding in mutant SOD1 could serve as an effective treatment of ALS. Here, I briefly review the copper and zinc binding process of SOD1 and discuss a copper chaperone for SOD1 as a potential target for developing ALS therapeutics.

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