The accumulation of enzymatically inactive cuproenzymes is a CNS-specific phenomenon of the SOD1 G37R mouse model of ALS and can be restored by overexpressing the human copper transporter hCTR1

Abstract

Mutations to the copper-dependent enzyme Cu/Zn-superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS) in humans, and transgenic overexpression of mutant SOD1 represents a robust murine model of the disease. We have previously shown that the copper-containing compound Cu II (atsm) phenotypically improves mutant SOD1 mice and delivers copper to copper-deficient SOD1 in the CNS to restore its physiological function. Cu II (atsm) is now in clinical trials for the treatment of ALS. In this study, we demonstrate that cuproenzyme dysfunction extends beyond SOD1 in SOD1 G37R mice to also affect the endogenous copper-dependent ferroxidase ceruloplasmin. We show that SOD1 and ceruloplas..