{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:28:25Z","timestamp":1791361705423,"version":"4.3.1"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,8,27]],"date-time":"2013-08-27T00:00:00Z","timestamp":1377561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2013,9]]},"abstract":"Background and Purpose<\/jats:title>Amyotrophic lateral sclerosis (ALS<\/jats:styled-content>) is a fatal neurodegenerative disorder with no effective treatment. Fasudil hydrochloride (fasudil), a potent rho kinase (ROCK<\/jats:styled-content>) inhibitor, is useful for the treatment of ischaemic diseases. In previous reports, fasudil improved pathology in mouse models of A<\/jats:styled-content>lzheimer's disease and spinal muscular atrophy, but there is no evidence in that it can affect ALS<\/jats:styled-content>. We therefore investigated its effects on experimental models of ALS<\/jats:styled-content>.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>In mice motor neuron (NSC34<\/jats:styled-content>) cells, the neuroprotective effect of hydroxyfasudil (M3<\/jats:styled-content>), an active metabolite of fasudil, and its mechanism were evaluated. Moreover, the effects of fasudil, 30 and 100\u2009mg\u00b7kg\u22121<\/jats:sup>, administered via drinking water to mutant superoxide dismutase 1 (SOD1G93A<\/jats:sup><\/jats:styled-content>) mice were tested by measuring motor performance, survival time and histological changes, and its mechanism investigated.<\/jats:p><\/jats:sec>Key Results<\/jats:title>M3<\/jats:styled-content> prevented motor neuron cell death induced by SOD1G93A<\/jats:sup><\/jats:styled-content>. Furthermore, M3<\/jats:styled-content> suppressed both the increase in ROCK<\/jats:styled-content> activity and phosphorylated phosphatase and tensin homologue deleted on chromosome 10 (PTEN<\/jats:styled-content>), and the reduction in phosphorylated Akt<\/jats:styled-content> induced by SOD1G93A<\/jats:sup><\/jats:styled-content>. These effects of M3<\/jats:styled-content> were attenuated by treatment with a PI3K<\/jats:styled-content> inhibitor (LY294002<\/jats:styled-content>). Moreover, fasudil slowed disease progression, increased survival time and reduced motor neuron loss, in SOD1G93A<\/jats:sup><\/jats:styled-content> mice. Fasudil also attenuated the increase in ROCK<\/jats:styled-content> activity and PTEN<\/jats:styled-content>, and the reduction in A<\/jats:styled-content>kt in SOD1G93A<\/jats:sup><\/jats:styled-content> mice.<\/jats:p><\/jats:sec>Conclusions and Implications<\/jats:title>These findings indicate that fasudil may be effective at suppressing motor neuron degeneration and symptom progression in ALS<\/jats:styled-content>. Hence, fasudil may have potential as a therapeutic agent for ALS<\/jats:styled-content> treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12277","type":"journal-article","created":{"date-parts":[[2013,6,14]],"date-time":"2013-06-14T06:24:53Z","timestamp":1371191093000},"page":"341-351","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":122,"title":["Fasudil, a rho kinase inhibitor, limits motor neuron loss in experimental models of amyotrophic lateral sclerosis"],"prefix":"10.1111","volume":"170","author":[{"given":"M","family":"Takata","sequence":"first","affiliation":[{"name":"Molecular Pharmacology Department of Biofunctional Evaluation Gifu Pharmaceutical University Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Molecular Pharmacology Department of Biofunctional Evaluation Gifu Pharmaceutical University Gifu 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