SOD1 - copper zinc superoxide dismutase 1 and ALS
Further research into the role of SOD1 and of protein aggregates in neurodegenerative diseases should settle the debate and allow for design of appropriate therapies.
The potential for transition metal-mediated neurodegeneration in amyotrophic lateral sclerosis
https://www.ncbi.nlm.nih.gov/pubmed/25100994
The discovery of mutations in the antioxidant enzyme Cu/Zn superoxide dismutase 1 (SOD-1) in ALS patients established the first known cause of ALS. Recent data suggest that various mutations in SOD-1 affect metal-binding of Cu and Zn, in turn promoting toxic protein aggregation. Copper homeostasis is also disturbed in ALS, and may be relevant to ALS pathogenesis.
Structure, folding, and misfolding of Cu,Zn superoxide dismutase in amyotrophic lateral sclerosis
http://www.sciencedirect.com/science/article/pii/S0925443906000846
Fourteen years after the discovery that mutations in Cu, Zn superoxide dismutase (SOD1) cause a subset of familial amyotrophic lateral sclerosis (fALS), the mechanism by which mutant SOD1 exerts toxicity remains unknown. The two principal hypotheses are (a) oxidative damage stemming from aberrant SOD1 redox chemistry, and (b) misfolding of the mutant protein
Metal dyshomeostasis and oxidative stress in Alzheimer's disease.
https://www.ncbi.nlm.nih.gov/pubmed/22982299
Accumulating evidence suggests that copper, zinc, and iron homeostasis may become perturbed in Alzheimer's disease and could underlie an increased oxidative stress burden. In this review we discuss oxidative/nitrosative stress in Alzheimer's disease with a focus on the role that metals play in this process.
Activation of superoxide dismutases: Putting the metal to the pedal
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1633718/
The most widely studied connection between SOD1 and human diseases involves the late onset neurodegenerative disease ALS. Over one hundred mutations in the human gene SOD1 are now known to lead to some of the inherited forms of ALS, and several outstanding reviews cover the physiology and biochemical mechanisms that are under evaluation.
Amyotrophic lateral sclerosis and structural defects in Cu,Zn superoxide dismutase.
https://www.ncbi.nlm.nih.gov/pubmed/8351519/
Single-site mutants in the Cu,Zn superoxide dismutase (SOD) gene (SOD1) occur in patients with the fatal neurodegenerative disorder familial amyotrophic lateral sclerosis (FALS). Red cells from heterozygotes had less than 50 percent normal SOD activity, consistent with a structurally defective SOD dimer. Thus, defective SOD is linked to motor neuron death and carries implications for understanding and possible treatment of FALS.
Disturbed copper bioavailability in Alzheimer's disease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227474/
In a clinical trial with Alzheimer patients, the decline of Aβ levels in CSF, which is a diagnostic marker, is diminished in the verum group (8 mg copper/day), indicating a beneficial effect of the copper treatment. These observations are in line with the benefit of treatment with compounds aimed at normalizing metal levels in the brain, such as PBT2
Superoxide dismutase and catalase activity in psoriatic patients treated topically with ointment containing 2-chloroethyl-3-chloropropyl sulfide.
https://www.ncbi.nlm.nih.gov/pubmed/7894531
Applied on psoriatic skin, causes increased of SOD and CAT activity in erythrocytes after regression of psoriatic lesions and treatment termination.
Blood metalloproteins of pro-oxidant and antioxidant action in psoriasis
https://www.ncbi.nlm.nih.gov/pubmed/10445277
Mechanism of pathogenesis of psoriasis related with intensity of formation of oxygen active forms high concentration, depends on balance of pro-oxidant and antioxidant systems activity.
Positive Clinical Study Results Reported by Adeona's Oral Zinc for ALS Collaborator
https://clinicaltrials.gov/ct2/show/NCT01259050
The clinical study met its primary outcome as no safety issues related to zinc therapy were observed. We are pleased to report that the use of zinc is safe in ALS patients, and we are also encouraged to observe that this small group of ALS patients demonstrated a reduced rate of change in their ALSFRS-R scores while taking zinc, suggesting a slower rate of disease progression. Adeona's proprietary zinc-based therapy that has already demonstrated clinical evidence of being very well tolerated by patients and of providing superior bioavailability."
ALS Clinical Study using diacetylbis(N(4)-methylthiosemicarbazonato) copper(II)
https://clinicaltrials.gov/ct2/show/NCT03136809
Treatment extension study for ALS/MND patients who participated in phase 1 study CMD-2016-001, completed assessments following six 28-day cycles of treatment, and whom the Investigator considers would benefit from continued Cu treatment.