Enhanced Neurite Outgrowth of Human Model (NT2) Neurons by Small-Molecule Inhibitors of Rho/ROCK Signaling
| العنوان: | Enhanced Neurite Outgrowth of Human Model (NT2) Neurons by Small-Molecule Inhibitors of Rho/ROCK Signaling |
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| المؤلفون: | Gerd Bicker, Michael Stern, Carola Dewitz, Frank Roloff, Hannah Scheiblich, Silke Dempewolf |
| المصدر: | PLoS ONE, Vol 10, Iss 2, p e0118536 (2015) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Nervous system, RHOA, Neurite, Cell Survival, lcsh:Medicine, Cell Line, chemistry.chemical_compound, Lysophosphatidic acid, Neurites, medicine, Humans, Axon, lcsh:Science, Protein Kinase Inhibitors, Rho-associated protein kinase, Neurons, rho-Associated Kinases, Multidisciplinary, biology, lcsh:R, Cell biology, Enzyme Activation, medicine.anatomical_structure, nervous system, chemistry, biology.protein, lcsh:Q, Neuron, Collapsin response mediator protein family, Signal Transduction, Research Article |
| الوصف: | 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. |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::68240f5c34db58e3d126a2a996d21be3Test https://doi.org/10.1371/journal.pone.0118536Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....68240f5c34db58e3d126a2a996d21be3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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