We propose that stabilizing the functional loops within SOD1 and/or obscuring the C4F6 epitope are viable therapeutic strategies for treating SOD1-mediated ALS.
ALS-associated mutant SOD1G93A causes mitochondrial vacuolation by expansion of the intermembrane space and by involvement of SOD1 aggregation and peroxisomes.
Mutations in Cu/Zn superoxide dismutase-1 (SOD1) cause familial ALS but the molecular mechanisms whereby these mutations induce motor neuron death remain controversial.
Evidence from patients with sporadic and familiar amyotrophic lateral sclerosis (ALS) and from models based on the overexpression of mutant SOD1 found in a small subset of patients, clearly point to mitochondrial damage as a relevant facet of this neurodegenerative condition.
Lack of synergistic effect of resveratrol and sigma-1 receptor agonist (PRE-084) in SOD1G⁹³A ALS mice: overlapping effects or limited therapeutic opportunity?
These results suggest that EBGP containing the active ingredient against mutant SOD1-mediated toxicity is a promising medicine or health food for prevention and treatment of ALS.
In the present study, we investigated neurodegenerative changes including neuronal loss and glia pathology in the anterodorsal thalamic nucleus (AD) of SOD1(G93A) mice, a widely used animal model for ALS.
Interestingly, mutant FUS-induced impairment of FAT in squid axoplasm and of axonal outgrowth in mammalian primary motor neurons involved aberrant activation of the p38 MAPK pathway, as also reported for ALS-linked forms of Cu, Zn superoxide dismutase (SOD1).
The findings show that wild-type human superoxide dismutase-1 has the ability to cause ALS in mice, and they support the hypothesis of a more general involvement of the protein in the disease in humans.
Here, we report that two independent ALS-linked autophagy-associated gene products; SQSTM1/p62 and ALS2/alsin, but not antioxidant-related factor; NFE2L2/Nrf2, are implicated in the pathogenesis in mutant SOD1 transgenic ALS models.
Several ALS genes have been identified as their mutations can lead to familial ALS, including the recently reported RNA-binding protein fused in sarcoma (Fus).
The neurotoxin β-<i>N</i>-methylamino-l-alanine (BMAA), a non-protein amino acid produced by terrestrial and aquatic cyanobacteria and by micro-algae, has been suggested to play a role as an environmental factor in the neurodegenerative disease Amyotrophic Lateral Sclerosis-Parkinsonism-Dementia complex (ALS-PDC).
Denaturational stress induces formation of zinc-deficient monomers of Cu,Zn superoxide dismutase: implications for pathogenesis in amyotrophic lateral sclerosis.
Our findings first demonstrate that small-diameter DRG neurons of the ALS mouse model SOD1(G93A)display axonal stress in vitro and in vivo, thus sustaining the hypothesis that the effects of ALS disease spread beyond motor neurons.
Presymptomatic biochemical changes in hindlimb muscle of G93A human Cu/Zn superoxide dismutase 1 transgenic mouse model of amyotrophic lateral sclerosis.
The comparability of the findings in sALS patients and in the hSOD1-G93A transgenic mouse model suggests that the examined genes may play a specific role in the pathogenesis of ALS.