Copper-Zinc Superoxide Dismutase and Amyotrophic Lateral Sclerosis

Abstract

Copper-zinc superoxide dismutase (CuZnSOD, SOD1 protein) is an abundant copper- and zinc-containing protein that is present in the cytosol, nucleus, peroxisomes, and mitochondrial intermembrane space of human cells. Its primary function is to act as an antioxidant enzyme, lowering the steady-state concentration of superoxide, but when mutated, it can also cause disease. Over 100 different mutations have been identified in the sod1 genes of patients diagnosed with the familial form of amyotrophic lateral sclerosis (fALS). These mutations result in a highly diverse group of mutant proteins, some of them very similar to and others enormously different from wild-type SOD1. Despite their differences in properties, each member of this diverse set of mutant proteins causes the same clinical disease, presenting a challenge in formulating hypotheses as to what causes SOD1-associated fALS. In this review, we draw together and summarize information from many laboratories about the characteristics of the individual mutant SOD1 proteins in vivo and in vitro in the hope that it will aid investigators in their search for the cause(s) of SOD1-associated fALS.

Proteomic identification of brain proteins in the canine model of human aging following a long-term treatment with antioxidants and a program of behavioral enrichment: Relevance to Alzheimer's disease

“…Cu/Zn Superoxide dismutase (CuZnSOD, SOD1 protein) is an abundant copper-and zinccontaining protein that is present in the cytosol, nucleus, peroxisomes, and mitochondrial intermembrane space of human cells and acts as an antioxidant enzyme by lowering the steadystate concentration of superoxide [97]. When mutated, SOD can also cause disease as in the case of the neurodegenerative disorder, familial amyotrophic lateral sclerosis (fALS) [97].…”

“…When mutated, SOD can also cause disease as in the case of the neurodegenerative disorder, familial amyotrophic lateral sclerosis (fALS) [97]. The toxic gain of function of mutant SOD (mSOD) leads to the generation of reactive oxygen/ nitrogen species [83,91,114].…”

Elevated oxidative stress in erythrocytes due to a SOD1 deficiency causes anaemia and triggers autoantibody production

“…Constitutive SOD1 expression is a normal occurrence in most tissues, except for keratinocytes and glomerular mesangial cells in which nitrosoglutathione induces SOD1 expression [2,3], while SOD2 expression is regulated by a variety of agents, including inflammatory cytokines, lipopolysaccharide and oxidative stress [4,5]. The SOD1 protein is localized in the cytosol and the intermembrane space of mitochondria, whereas the SOD2 protein is exclusively located in mitochondria [6,7].…”

Oxidative and excitotoxic insults exert differential effects on spinal motoneurons and astrocytic glutamate transporters: Implications for the role of astrogliosis in amyotrophic lateral sclerosis

“…Amyotrophic lateral sclerosis (ALS) is characterized by the selective and progressive loss of motoneurons in motor cortex, brainstem, and spinal cord (Valentine et al, 2005). Although the loss of motoneurons is the direct cause of motor symptoms, the noncell-autonomous hypothesis of ALS attributes a role to non-neuronal cells in disease etiology (Boillee et al, 2006).…”