S134N copper-zinc superoxide dismutase (SOD1) is one of the many mutant SOD1 proteins known to cause familial amyotrophic lateral sclerosis. Earlier studies demonstrated that partially metal-deficient S134N SOD1 crystallized in filament-like arrays with abnormal contacts between the individual protein molecules. Because protein aggregation is implicated in SOD1-linked familial amyotrophic later...

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by motoneuron loss. Some familial cases (fALS) are linked to mutations of superoxide dismutase type-1 (SOD1), an antioxidant enzyme whose activity is preserved in most mutant forms. Owing to the similarities in sporadic and fALS forms, mutant SOD1 animal and cellular models are a useful tool to study the disease. In trans...

Mutations in copper/zinc superoxide dismutase (SOD1) are causative for dominantly inherited amyotrophic lateral sclerosis (ALS). Despite high variability in biochemical properties among the disease-causing mutants, a proportion of both dismutase-active and -inactive mutants are stably bound to spinal cord mitochondria. This mitochondrial proportion floats with mitochondria rather than sedimenti...

Mutation in superoxide dismutase 1 (SOD1), a Cu/Zn enzyme that removes oxygen radicals and protects against oxidative injury, has been implicated in some cases of familial amyotrophic lateral sclerosis (FALS). As a first approach to examining the mechanism(s) through which these mutations cause specific degeneration of motor neurons, we have used immunocytochemistry to identify the distribution...

The death of cranial and spinal motoneurons (MNs) is believed to be an essential component of the pathogenesis of amyotrophic lateral sclerosis (ALS). We tested this hypothesis by crossing Bax-deficient mice with mice expressing mutant superoxide dismutase 1 (SOD1), a transgenic model of familial ALS. Although Bax deletion failed to prevent neuromuscular denervation and mitochondrial vacuolizat...

Saccharomyces cerevisiae mutants deficient in superoxide dismutase genes (sod1∆, sod2∆ and the double mutant) were subjected to H2O2 stress in the stationary phase. The highest sensitivity was observed in the sod2∆ mutant, while the sod1∆sod2∆ double mutant was not sensitive. sod mutants had lower catalase activity (44%) than wildtype cells, independent of H2O2 stress. Untreated cells of sod1∆s...

Mutations in superoxide dismutase 1 (SOD1) cause familial ALS. Mutant SOD1 preferentially associates with the cytoplasmic face of mitochondria from spinal cords of rats and mice expressing SOD1 mutations. Two-dimensional gels and multidimensional liquid chromatography, in combination with tandem mass spectrometry, revealed 33 proteins that were increased and 21 proteins that were decreased in S...

"Prion-like propagation" has recently been proposed for disease spread in Cu/Zn superoxide dismutase 1 (SOD1)-linked familial amyotrophic lateral sclerosis (ALS). Pathological SOD1 conformers are presumed to propagate via cell-to-cell transmission. In this model, the risk-based kinetics of neuronal cell loss over time appears to be represented by a sigmoidal function that reflects the kinetics ...

Transgenic mice expressing high levels of familial amyotrophic lateral sclerosis (FALS)-associated mutant superoxide dismutase 1 (SOD1) under the control of a human SOD1 minigene (hMg) accumulate mutant protein ubiquitously and develop motoneuron disease. However, restricted expression of SOD1 mutants in neurons apparently does not cause motor impairments in mice. Here, we investigated the poss...

The transplantation of neural stem cells (NSCs) has been demonstrated as a potential treatment strategy for traumatic brain injury (TBI). Cu, Zn-superoxide dismutase (SOD1) is an important antioxidant enzyme that detoxifies intracellular reactive oxygen species, thereby protecting cells from oxidative damage. PEP-1, a peptide carrier, is able to deliver full-length native peptides or proteins i...