We are analyzing https://link.springer.com/article/10.1007/s12640-016-9677-6.

Title:
A Novel Iron Chelator-Radical Scavenger Ameliorates Motor Dysfunction and Improves Life Span and Mitochondrial Biogenesis in SOD1G93A ALS Mice | Neurotoxicity Research
Description:
The aim of the present study was to evaluate the therapeutic effect of the novel neuroprotective multitarget brain permeable monoamine oxidase inhibitor/iron chelating-radical scavenging drug, VAR10303 (VAR), co-administered with high-calorie/energy-supplemented diet (ced) in SOD1G93A transgenic amyotrophic lateral sclerosis (ALS) mice. Administration of VAR-ced was initiated after the appearance of disease symptoms (at day 88), as this regimen is comparable with the earliest time at which drug therapy could start in ALS patients. Using this rescue protocol, we demonstrated in the current study that VAR-ced treatment provided several beneficial effects in SOD1G93A mice, including improvement in motor performance, elevation of survival time, and attenuation of iron accumulation and motoneuron loss in the spinal cord. Moreover, VAR-ced treatment attenuated neuromuscular junction denervation and exerted a significant preservation of myofibril regular morphology, associated with a reduction in the expression levels of genes related to denervation and atrophy in the gastrocnemius (GNS) muscle in SOD1G93A mice. These effects were accompanied by upregulation of mitochondrial DNA and elevated activities of complexes I and II in the GNS muscle. We have also demonstrated that VAR-ced treatment upregulated the mitochondrial biogenesis master regulator, peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α) and increased PGC-1α-targeted metabolic genes and proteins, such as, PPARγ, UCP1/3, NRF1/2, Tfam, and ERRα in GNS muscle. These results provide evidence of therapeutic potential of VAR-ced in SOD1G93A mice with underlying molecular mechanisms, further supporting the importance role of multitarget iron chelators in ALS treatment.
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Keywords {🔍}

pubmed, article, google, scholar, cas, lateral, sclerosis, amyotrophic, iron, central, muscle, mice, disease, model, mouse, motor, mitochondrial, sodga, youdim, transgenic, amit, skeletal, sci, weinreb, res, research, biogenesis, baram, neuroprotective, patients, effects, neurosci, neurol, privacy, cookies, content, study, varced, cord, expression, access, chelator, cells, neuron, pgc, dois, function, publish, search, life,

Topics {✒️}

peroxisome proliferator-activated receptor-γ month download article/chapter high-calorie/energy-supplemented diet central nervous system multimodal iron-chelating drugs iron-chelating drugs m30 pgc-1alpha protects neurons article golko-perez multitarget iron chelator slow-twitch muscle fibres studying muscle-neuron communication var-ced treatment provided var-ced treatment upregulated early motor-neuron degeneration /monoamine oxidase full article pdf amyotrophic lateral sclerosis multitarget iron chelators brain iron accumulation virus encoding bcl-2 c2c12 murine myoblasts pgc-1alpha signaling rappaport family research increased motoneuron survival privacy choices/manage cookies compartmental microfluidic system motor neuron degeneration sod1g93a transgenic mice neuromuscular junction maintenance inappropriately chelated iron sod1g93a als mice amyotroph lateral scler age-related alterations activated protein iron chelating defective mitochondrial dynamics apparent motor deficit youdim & orly weinreb related subjects low grade inflammation migf-1 modulates ubiquitin transgenic als mice skeletal muscle development potential neuroprotective agents technion israel institute technion-israel institute preclinical drug studies european economic area myofibril regular morphology results provide evidence

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