ArticleCell death & disease2014
ROCK2 is a major regulator of axonal degeneration, neuronal death and axonal regeneration in the CNS.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
105 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Frontiers of optic nerve regeneration research: an analysis of the top 100 most influential articles in the field from 2005 to 2025.Frontiers in neuroscience · 2025Pooled it
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Trial
- Adeno-associated virus-mediated inhibition of ROCK2 promotes synaptogenesis and neurogenesis in rats after ischemic stroke.Neural regeneration research · 2026Article
- Autophagy-Induced Microglial Death Contributes to Neuroinflammation in Acute Optic Nerve Injury.Investigative ophthalmology & visual science · 2025Article
- Article
- Rho kinase isoforms in neurodegeneration: from cellular functions to therapeutic targets.Molecular biology reports · 2025Review
- Comparative transcriptome analysis of pectoralis major muscles affected by white striping, wooden breast and spaghetti meat in male and female broiler chickens.BMC genomics · 2025Article
- Review
- Effects of a ROCK Inhibitor on Retinal Ganglion Cells In Vivo and In Vitro.Journal of clinical medicine · 2025Article
- Total Flavones ofCurrent issues in molecular biology · 2025Article
- Fasudil protects spiral ganglion neurons and hair cells against cisplatin-induced apoptosis by inhibiting reactive oxygen species accumulation and regulating the ROCK/PTEN/AKT signaling pathway.Toxicology research · 2025Article
- Identification of Sequential Molecular Mechanisms and Key Biomarkers in Early Glaucoma by Integrated Bioinformatics Analysis.Molecular neurobiology · 2025Article
- Novel insights into the ROCK-JAK-STAT signaling pathway in upper respiratory tract infections and neurodegenerative diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- The role of RGC degeneration in the pathogenesis of glaucoma.International journal of biological sciences · 2025Review
- Rho/ROCK Pathway as a Therapeutic Target in Multiple Diseases.International journal of drug discovery and pharmacology · 2025Article
- A Scoping Review of Rho Kinase Inhibitors and their Role in Glaucoma Treatment.Current medicinal chemistry · 2025Article
- Understanding neurodevelopmental proteasomopathies as new rare disease entities: A review of current concepts, molecular biomarkers, and perspectives.Genes & diseases · 2024Review
- The Axonal Actin Filament Cytoskeleton: Structure, Function, and Relevance to Injury and Degeneration.Molecular neurobiology · 2024Review
- HMolecular neurobiology · 2024Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Rho/ROCK/LIMK pathway is central for the mediation of repulsive environmental signals in the central nervous system. Several studies using pharmacological Rho-associated protein kinase (ROCK) inhibitors have shown positive effects on neurite regeneration and suggest additional pro-survival effects in neurons. However, as none of these drugs is completely target specific, it remains unclear how these effects are mediated and whether ROCK is really the most relevant target of the pathway. To answer these questions, we generated adeno-associated viral vectors to specifically downregulate ROCK2 and LIM domain kinase (LIMK)-1 in rat retinal ganglion cells (RGCs) in vitro and in vivo. We show here that specific knockdown of ROCK2 and LIMK1 equally enhanced neurite outgrowth of RGCs on inhibitory substrates and both induced substantial neuronal regeneration over distances of more than 5 mm after rat optic nerve crush (ONC) in vivo. However, only knockdown of ROCK2 but not LIMK1 increased survival of RGCs after optic nerve axotomy. Moreover, knockdown of ROCK2 attenuated axonal degeneration of the proximal axon after ONC assessed by in vivo live imaging. Mechanistically, we demonstrate here that knockdown of ROCK2 resulted in decreased intraneuronal activity of calpain and caspase 3, whereas levels of pAkt and collapsin response mediator protein 2 and autophagic flux were increased. Taken together, our data characterize ROCK2 as a specific therapeutic target in neurodegenerative diseases and demonstrate new downstream effects of ROCK2 including axonal degeneration, apoptosis and autophagy.
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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.