Mutations in the gene superoxide dismutase 1 (SOD1) are causative for familial forms of the neurodegenerative disease amyotrophic lateral sclerosis. When the first SOD1 mutations were identified they were postulated to give rise to amyotrophic lateral sclerosis through a loss of function mechanism, but experimental data soon showed that the disease arises from a—still unknown—toxic gain of func...

Amyotrophic lateral sclerosis (ALS) is a fatal degenerative motor neuron disease. Approximately 20 percent of familial ALS cases are caused by mutations in the Cu/Zn superoxide dismutase (SOD1) gene. Rodents expressing mutant SOD1 transgenes develop progressive, fatal motor neuron disease and disease onset and progression is dependent on the level of SOD1. We investigated the possibility that a...

Copper–zinc superoxide dismutase (SOD1) is an antioxidant found in cytoplasm. Many different mutations in SOD1 have been linked to familial amyotrophic lateral sclerosis (ALS), a neurodegenerative disease in which increasing motor neuron failure proves fatal. SOD1 aggregates have been found in human spinal cords during autopsies; in mice, similar aggregates are known to have a fibrillar nature ...

In contrast to other mouse models that are deficient in antioxidant enzymes, mice null for Cu/Zn-superoxide dismutase (Sod1-/- mice) show a major decrease in lifespan and several accelerated aging phenotypes. The goal of this study was to determine if cell senescence might be a contributing factor in the accelerated aging phenotype observed in the Sod1-/- mice. We focused on kidney because it i...

Pambo-Pambo A, Durand J, Gueritaud JP. Early excitability changes in lumbar motoneurons of transgenic SOD1 and SOD1 mice. J Neurophysiol 102: 3627–3642, 2009. First published October 14, 2009; doi:10.1152/jn.00482.2009. This work characterizes the properties of wild-type (WT) mouse motoneurons in the second postnatal week and compares these at the same age and in the same conditions to those of...

IMS (intermembrane space) SOD1 (Cu/Zn-superoxide dismutase) is inactive in isolated intact rat liver mitochondria and is activated following oxidative modification of its critical thiol groups. The present study aimed to identify biochemical pathways implicated in the regulation of IMS SOD1 activity and to assess the impact of its functional state on key mitochondrial events. Exogenous H2O2 (5 ...

Mutations in the gene superoxide dismutase 1 (SOD1) are causative for familial forms of the neurodegenerative disease amyotrophic lateral sclerosis. When the first SOD1 mutations were identified they were postulated to give rise to amyotrophic lateral sclerosis through a loss of function mechanism, but experimental data soon showed that the disease arises from a--still unknown--toxic gain of fu...

Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease causing death of motor neurons. This study investigated the roles of energy metabolism in the pathogenesis of ALS in the SOD1(G93A) transgenic mouse model. Control and SOD1(G93A) mice were administered with shcontrol or shPGC-1α in combination with PBS or thiazolidinedione (TZD) for 8 weeks. Gene expression was analyzed b...

Mutations in superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS), an adult-onset progressive paralytic disease characterized by loss of motor neurons, and cause an ALS-like disease when expressed in mice. Recent data have suggested that motor neuron degeneration results from toxic actions of mutant SOD1 operating in both motor neurons and their neighboring glia, raising the qu...

A prion-like mechanism has been developed to explain the observed promotion of amyloid aggregation caused by conversion of structurally intact SOD1 to a misfolded form. Superoxide dismutase [Cu-Zn], or SOD1, is a homo-dimeric protein that functions as an antioxidant by scavenging for superoxide. The misfolding and aggregation of SOD1 is linked to inherited, or familial, amyotrophic lateral scle...