ArticleBrain : a journal of neurology2012
Inhibition of rho kinase enhances survival of dopaminergic neurons and attenuates axonal loss in a mouse model of Parkinson's disease.
Article in Brain : a journal of neurology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 170 citations in OpenAlex.
- Trial
- Adeno-associated virus-mediated inhibition of ROCK2 promotes synaptogenesis and neurogenesis in rats after ischemic stroke.Neural regeneration research · 2026Article
- RhoA/ROCK signaling as a potential convergent pathway in microbiota-gut-brain axis-related cognitive impairment.Frontiers in neurology · 2026Review
- Rho kinase isoforms in neurodegeneration: from cellular functions to therapeutic targets.Molecular biology reports · 2025Review
- Mechanisms of angiotensin II to induce depression in diabetes.Diabetology international · 2025Review
- Gastrodin Mitigates Ketamine-Induced Inhibition of F-Actin Remodeling and Cell Migration by Regulating the Rho Signaling Pathway.Biomedicines · 2025Article
- Fasudil inhibits α-synuclein aggregation through ROCK-inhibition-mediated mechanisms.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- New insights on the regulators and inhibitors of RhoA-ROCK signalling in Parkinson's disease.Metabolic brain disease · 2025Review
- RhoA/ROCK2 signaling pathway regulates Mn-induced alterations in tight junction proteins leading to cognitive dysfunction in mice.Current research in toxicology · 2025Article
- Evaluating the Role of Lin-11, Isl-1, and Mec-3 Kinases in Dopaminergic Neurodegeneration in a Subacute 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Model of Parkinson's Disease.ACS pharmacology & translational science · 2024Article
- Article
- Behavioral analysis of motor and non-motor impairment in rodent models of Parkinson's disease.Frontiers in aging neuroscience · 2024Review
- Protocol for a randomized, placebo-controlled, double-blind phase IIa study of the safety, tolerability, and symptomatic efficacy of the ROCK-inhibitor Fasudil in patients with Parkinson's disease (ROCK-PD).Frontiers in aging neuroscience · 2024Article
- Role of Rho-associated kinases and their inhibitor fasudil in neurodegenerative diseases.Frontiers in neuroscience · 2024Review
- Crosstalk between the Rho and Rab family of small GTPases in neurodegenerative disorders.Frontiers in cellular neuroscience · 2023Review
- Cell Biology of Parkin: Clues to the Development of New Therapeutics for Parkinson's Disease.CNS drugs · 2022Review
- Screen identifies fasudil as a radioprotector on human fibroblasts.Toxicology research · 2022Article
- ROCK and PDE-5 Inhibitors for the Treatment of Dementia: Literature Review and Meta-Analysis.Biomedicines · 2022Review
- RhoA Signaling in Neurodegenerative Diseases.Cells · 2022Review
- Rnd3 Expression is Necessary to Maintain Mitochondrial Homeostasis but Dispensable for Autophagy.Frontiers in cell and developmental biology · 2022Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Axonal degeneration is one of the earliest features of Parkinson's disease pathology, which is followed by neuronal death in the substantia nigra and other parts of the brain. Inhibition of axonal degeneration combined with cellular neuroprotection therefore seem key to targeting an early stage in Parkinson's disease progression. Based on our previous studies in traumatic and neurodegenerative disease models, we have identified rho kinase as a molecular target that can be manipulated to disinhibit axonal regeneration and improve survival of lesioned central nervous system neurons. In this study, we examined the neuroprotective potential of pharmacological rho kinase inhibition mediated by fasudil in the in vitro 1-methyl-4-phenylpyridinium cell culture model and in the subchronic in vivo 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. Application of fasudil resulted in a significant attenuation of dopaminergic cell loss in both paradigms. Furthermore, dopaminergic terminals were preserved as demonstrated by analysis of neurite network in vitro, striatal fibre density and by neurochemical analysis of the levels of dopamine and its metabolites in the striatum. Behavioural tests demonstrated a clear improvement in motor performance after fasudil treatment. The Akt survival pathway was identified as an important molecular mediator for neuroprotective effects of rho kinase inhibition in our paradigm. We conclude that inhibition of rho kinase using the clinically approved small molecule inhibitor fasudil may be a promising new therapeutic strategy for Parkinson's disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.