ArticlePloS one2015
Enhanced neurite outgrowth of human model (NT2) neurons by small-molecule inhibitors of Rho/ROCK signaling.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 57 citations in OpenAlex.
- Impact of ibuprofen and peroxisome proliferator-activated receptor gamma on emotion-related neural activation: A randomized, placebo-controlled trial.Brain, behavior, and immunity · 2021Trial
- Unraveling the Morphological and Functional Maturation Mechanisms Underlying Human Neural Development Using iPSCs-Derived Neuronal Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- MicroRNAs in Tissue Regeneration: Lessons from Animal Models.International journal of molecular sciences · 2025Review
- The potential of baicalin to enhance neuroprotection and mitochondrial function in a human neuronal cell model.Molecular psychiatry · 2024Article
- Neurotoxicity and Developmental Neurotoxicity of Copper Sulfide Nanoparticles on a Human Neuronal In-Vitro Test System.International journal of molecular sciences · 2024Article
- Activation of S1PCell proliferation · 2024Article
- Article
- Improved Cryopreservation of Human Induced Pluripotent Stem Cell (iPSC) and iPSC-derived Neurons Using Ice-Recrystallization Inhibitors.Stem cells (Dayton, Ohio) · 2023Article
- Modeling Central Nervous System Injury In Vitro: Current Status and Promising Future Strategies.Biomedicines · 2022Review
- Protection against Hypoxia-Reoxygenation Injury of Hippocampal Neurons by HMolecules (Basel, Switzerland) · 2022Article
- Review
- Hypomyelinating Leukodystrophy 8 (HLD8)-Associated Mutation of POLR3B Leads to Defective Oligodendroglial Morphological Differentiation Whose Effect Is Reversed by Ibuprofen.Neurology international · 2022Article
- Looking at Developmental Neurotoxicity Testing from the Perspective of an Invertebrate Embryo.International journal of molecular sciences · 2022Review
- Ibuprofen does not inhibit RhoA-mediated growth cone collapse of embryonic chicken retinal axons by LPA.Experimental brain research · 2021Article
- Developmental Neurotoxicity of Fipronil and Rotenone on a Human Neuronal In Vitro Test System.Neurotoxicity research · 2021Article
- Y-27632 Induces Neurite Outgrowth by Activating the NOX1-Mediated AKT and PAK1 Phosphorylation Cascades in PC12 Cells.International journal of molecular sciences · 2020Article
- Protein kinases: master regulators of neuritogenesis and therapeutic targets for axon regeneration.Cellular and molecular life sciences : CMLS · 2020Review
- A method to rapidly analyze the simultaneous release of multiple pharmaceuticals from electrospun fibers.International journal of pharmaceutics · 2020Article
- Tanshinone IIA Promotes Axonal Regeneration in Rats with Focal Cerebral Ischemia Through the Inhibition of Nogo-A/NgR1/RhoA/ROCKII/MLC Signaling.Drug design, development and therapy · 2020Article
- Structural and Functional Plasticity in the Regenerating Olfactory System of the Migratory Locust.Frontiers in physiology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Axonal injury in the adult human central nervous system often results in loss of sensation and motor functions. Promoting regeneration of severed axons requires the inactivation of growth inhibitory influences from the tissue environment and stimulation of the neuron intrinsic growth potential. Especially glial cell derived factors, such as chondroitin sulfate proteoglycans, Nogo-A, myelin-associated glycoprotein, and myelin in general, prevent axon regeneration. Most of the glial growth inhibiting factors converge onto the Rho/ROCK signaling pathway in neurons. Although conditions in the injured nervous system are clearly different from those during neurite outgrowth in vitro, here we use a chemical approach to manipulate Rho/ROCK signalling with small-molecule agents to encourage neurite outgrowth in cell culture. The development of therapeutic treatments requires drug testing not only on neurons of experimental animals, but also on human neurons. Using human NT2 model neurons, we demonstrate that the pain reliever Ibuprofen decreases RhoA (Ras homolog gene family, member A GTPase) activation and promotes neurite growth. Inhibition of the downstream effector Rho kinase by the drug Y-27632 results in a strong increase in neurite outgrowth. Conversely, activation of the Rho pathway by lysophosphatidic acid results in growth cone collapse and eventually to neurite retraction. Finally, we show that blocking of Rho kinase, but not RhoA results in an increase in neurons bearing neurites. Due to its anti-inflammatory and neurite growth promoting action, the use of a pharmacological treatment of damaged neural tissue with Ibuprofen should be explored.
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