{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T07:09:15Z","timestamp":1778915355701,"version":"3.51.4"},"reference-count":13,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T00:00:00Z","timestamp":1633910400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T00:00:00Z","timestamp":1633910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000738","name":"u.s. department of veterans affairs","doi-asserted-by":"publisher","award":["IK2RX002688"],"award-info":[{"award-number":["IK2RX002688"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"name":"neurodegenerative disease research inc."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Brain"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Amyotrophic 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 (mSOD1<jats:sup>G93A<\/jats:sup>) mouse model of ALS during motor neuron degeneration and an in vitro model of mSOD1<jats:sup>G93A<\/jats:sup> motor neuron injury with bpV(pic) would prevent motor neuron loss. To test our hypothesis, we treated mSOD1<jats:sup>G93A<\/jats:sup> mice intraperitoneally daily with 400\u00a0\u03bcg\/kg bpV(pic) from 70 to 90\u00a0days 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 mSOD1<jats:sup>G93A<\/jats:sup> mice (<jats:italic>p<\/jats:italic>\u2009=\u20090.003) while not significantly altering microglial reactivity (<jats:italic>p<\/jats:italic>\u2009=\u20090.701). Treatment with bpV(pic) also significantly increased neuromuscular innervation (<jats:italic>p<\/jats:italic>\u2009=\u20090.018) but did not affect muscle atrophy. We also cultured motor neuron-like NSC-34 cells transfected with a plasmid to overexpress mutant SOD1<jats:sup>G93A<\/jats:sup> and starved them in serum-free medium for 24\u00a0h 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 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). In conclusion, our study indicates systemic bpV(pic) treatment could be a valuable neuroprotective therapy for ALS.<\/jats:p>","DOI":"10.1186\/s13041-021-00867-7","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T12:06:04Z","timestamp":1633953964000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Bisperoxovanadium promotes motor neuron survival and neuromuscular innervation in amyotrophic lateral sclerosis"],"prefix":"10.1186","volume":"14","author":[{"given":"Junmei","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lydia","family":"Tierney","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ranjeet","family":"Mann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Lonsway","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8616-8263","authenticated-orcid":false,"given":"Chandler L.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,10,11]]},"reference":[{"key":"867_CR1","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/B978-0-12-802973-2.00013-6","volume":"138","author":"EO Talbott","year":"2016","unstructured":"Talbott EO, Malek AM, Lacomis D. The epidemiology of amyotrophic lateral sclerosis. Handb Clin Neurol. 2016;138:225\u201338.","journal-title":"Handb Clin Neurol"},{"issue":"6","key":"867_CR2","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1093\/hmg\/ddx022","volume":"26","author":"MJ Stopford","year":"2017","unstructured":"Stopford MJ, Higginbottom A, Hautbergue GM, Cooper-Knock J, Mulcahy PJ, De Vos KJ, et al. C9ORF72 hexanucleotide repeat exerts toxicity in a stable, inducible motor neuronal cell model, which is rescued by partial depletion of Pten. Hum Mol Genet. 2017;26(6):1133\u201345.","journal-title":"Hum Mol Genet"},{"issue":"Pt 2","key":"867_CR3","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1093\/brain\/awq345","volume":"134","author":"J Kirby","year":"2011","unstructured":"Kirby J, Ning K, Ferraiuolo L, Heath PR, Ismail A, Kuo SW, et al. Phosphatase and tensin homologue\/protein kinase B pathway linked to motor neuron survival in human superoxide dismutase 1-related amyotrophic lateral sclerosis. Brain. 2011;134(Pt 2):506\u201317.","journal-title":"Brain"},{"issue":"2","key":"867_CR4","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/mt.2014.209","volume":"23","author":"D Little","year":"2015","unstructured":"Little D, Valori CF, Mutsaers CA, Bennett EJ, Wyles M, Sharrack B, et al. PTEN depletion decreases disease severity and modestly prolongs survival in a mouse model of spinal muscular atrophy. Mol Ther. 2015;23(2):270\u20137.","journal-title":"Mol Ther"},{"issue":"1","key":"867_CR5","doi-asserted-by":"publisher","first-page":"e30012","DOI":"10.1371\/journal.pone.0030012","volume":"7","author":"CL Walker","year":"2012","unstructured":"Walker CL, Walker MJ, Liu NK, Risberg EC, Gao X, Chen J, et al. Systemic bisperoxovanadium activates Akt\/mTOR, reduces autophagy, and enhances recovery following cervical spinal cord injury. PLoS ONE. 2012;7(1):e30012.","journal-title":"PLoS ONE"},{"key":"867_CR6","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.neulet.2014.02.039","volume":"573","author":"CL Walker","year":"2014","unstructured":"Walker CL, Xu XM. PTEN inhibitor bisperoxovanadium protects oligodendrocytes and myelin and prevents neuronal atrophy in adult rats following cervical hemicontusive spinal cord injury. Neurosci Lett. 2014;573:64\u20138.","journal-title":"Neurosci Lett"},{"issue":"18","key":"867_CR7","doi-asserted-by":"publisher","first-page":"2676","DOI":"10.1089\/neu.2018.6294","volume":"36","author":"CL Walker","year":"2019","unstructured":"Walker CL, Wu X, Liu NK, Xu XM. Bisperoxovanadium mediates neuronal protection through inhibition of PTEN and activation of PI3K\/AKT-mTOR signaling after traumatic spinal injuries. J Neurotrauma. 2019;36(18):2676\u201387.","journal-title":"J Neurotrauma"},{"issue":"3","key":"867_CR8","doi-asserted-by":"publisher","first-page":"302","DOI":"10.3109\/17482968.2012.662688","volume":"13","author":"R Mancuso","year":"2012","unstructured":"Mancuso R, Olivan S, Mancera P, Pasten-Zamorano A, Manzano R, Casas C, et al. Effect of genetic background on onset and disease progression in the SOD1-G93A model of amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2012;13(3):302\u201310.","journal-title":"Amyotroph Lateral Scler"},{"key":"867_CR9","doi-asserted-by":"crossref","unstructured":"Tung YT, Peng KC, Chen YC, Yen YP, Chang M, Thams S, et al. Mir-17-92 confers motor neuron subtype differential resistance to ALS-associated degeneration. 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