Fasudil, a rho kinase inhibitor, limits motor neuron loss in experimental models of amyotrophic lateral sclerosis.

摘要: Background and Purpose Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with no effective treatment. Fasudil hydrochloride (fasudil), potent rho kinase (ROCK) inhibitor, useful for the treatment of ischaemic diseases. In previous reports, fasudil improved pathology in mouse models Alzheimer's disease spinal muscular atrophy, but there evidence that it can affect ALS. We therefore investigated its effects on experimental ALS. Experimental Approach In mice motor neuron (NSC34) cells, neuroprotective effect hydroxyfasudil (M3), an active metabolite fasudil, mechanism were evaluated. Moreover, 30 100 mg·kg−1, administered via drinking water to mutant superoxide dismutase 1 (SOD1G93A) tested by measuring performance, survival time histological changes, investigated. Key Results M3 prevented cell death induced SOD1G93A. Furthermore, M3 suppressed both increase ROCK activity phosphorylated phosphatase tensin homologue deleted chromosome 10 (PTEN), reduction Akt These attenuated PI3K inhibitor (LY294002). slowed progression, increased reduced loss, SOD1G93A mice. also PTEN, mice. Conclusions Implications These findings indicate may be at suppressing degeneration symptom progression Hence, have potential as therapeutic agent ALS