Endogenous Cu in the central nervous system fails to satiate the elevated requirement for Cu in a mutant SOD1 mouse model of ALS

Abstract

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease, a fatal degenerative disorder in which motor neurons in the central nervous system (CNS) progressively deteriorate. Most cases of ALS are sporadic, but 10% are familial and mutations affecting the copper (Cu)-dependent antioxidant Cu/Zn-superoxide dismutase (SOD1) are the most common familial cause. Cu malfunction is evident in CNS tissue from transgenic mice that over-express mutant SOD1 and modulating Cu bioavailability in the CNS provides positive therapeutic outcomes. In the present study we assessed levels of Cu and Zn, SOD activity, and SOD1 protein levels in CNS and non-CNS tissue from transgenic muta..