Bisperoxovanadium promotes motor neuron survival and neuromuscular innervation in amyotrophic lateral sclerosis

dc.contributor.authorWang, Junmei
dc.contributor.authorTierney, Lydia
dc.contributor.authorMann, Ranjeet
dc.contributor.authorLonsway, Thomas
dc.contributor.authorWalker, Chandler L.
dc.contributor.departmentBiomedical Sciences and Comprehensive Care, School of Dentistryen_US
dc.date.accessioned2023-03-22T15:10:44Z
dc.date.available2023-03-22T15:10:44Z
dc.date.issued2021-10-11
dc.description.abstractAmyotrophic lateral sclerosis (ALS) is the most common motor neuron (MN) disease, with no present cure. The progressive loss of MNs is the hallmark of ALS. We have previously shown the therapeutic effects of the phosphatase and tensin homolog (PTEN) inhibitor, potassium bisperoxo (picolinato) vanadium (bpV[pic]), in models of neurological injury and demonstrated significant neuroprotective effects on MN survival. However, accumulating evidence suggests PTEN is detrimental for MN survival in ALS. Therefore, we hypothesized that treating the mutant superoxide dismutase 1 G93A (mSOD1G93A) mouse model of ALS during motor neuron degeneration and an in vitro model of mSOD1G93A motor neuron injury with bpV(pic) would prevent motor neuron loss. To test our hypothesis, we treated mSOD1G93A mice intraperitoneally daily with 400 μg/kg bpV(pic) from 70 to 90 days of age. Immunolabeled MNs and microglial reactivity were analyzed in lumbar spinal cord tissue, and bpV(pic) treatment significantly ameliorated ventral horn motor neuron loss in mSOD1G93A mice (p = 0.003) while not significantly altering microglial reactivity (p = 0.701). Treatment with bpV(pic) also significantly increased neuromuscular innervation (p = 0.018) but did not affect muscle atrophy. We also cultured motor neuron-like NSC-34 cells transfected with a plasmid to overexpress mutant SOD1G93A and starved them in serum-free medium for 24 h with and without bpV(pic) and downstream inhibitor of Akt signaling, LY294002. In vitro, bpV(pic) improved neuronal viability, and Akt inhibition reversed this protective effect (p < 0.05). In conclusion, our study indicates systemic bpV(pic) treatment could be a valuable neuroprotective therapy for ALS.en_US
dc.eprint.versionFinal published versionen_US
dc.identifier.citationWang J, Tierney L, Mann R, Lonsway T, Walker CL. Bisperoxovanadium promotes motor neuron survival and neuromuscular innervation in amyotrophic lateral sclerosis. Mol Brain. 2021;14(1):155. Published 2021 Oct 11. doi:10.1186/s13041-021-00867-7en_US
dc.identifier.urihttps://hdl.handle.net/1805/32011
dc.language.isoen_USen_US
dc.publisherBMCen_US
dc.relation.isversionof10.1186/s13041-021-00867-7en_US
dc.relation.journalMolecular Brainen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.sourcePMCen_US
dc.subjectAmyotrophic lateral sclerosisen_US
dc.subjectMotor neuronen_US
dc.subjectMuscular atrophyen_US
dc.subjectSuperoxide Dismutase-1en_US
dc.subjectNeuromuscular junctionen_US
dc.subjectVanadium compoundsen_US
dc.titleBisperoxovanadium promotes motor neuron survival and neuromuscular innervation in amyotrophic lateral sclerosisen_US
dc.typeArticleen_US
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