Título:
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Neurites regrowth of cortical neurons by GSK3b inhibition independently of Nogo Receptor 1
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Autor/a:
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Seira Oriach, Oscar; Gavín Marín, Rosalina; Gil, V.; Llorens Torres, Franc; Rangel, A.; Soriano García, Eduardo; Río Fernández, José Antonio del
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Otros autores:
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Universitat de Barcelona |
Abstract:
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Lesioned axons do not regenerate in the adult mammalian central nervous system, owing to the overexpression of inhibitory molecules such as myelin-derived proteins or chondroitin sulphate proteoglycans. In order to overcome axon inhibition, strategies based on extrinsic and intrinsic treatments have been developed. For myelin-associated inhibition, blockage with NEP1-40, receptor bodies or IN-1 antibodies has been used. In addition, endogenous blockage of cell signalling mechanisms induced by myelin-associated proteins is a potential tool for overcoming axon inhibitory signals. We examined the participation of glycogen synthase kinase 3 (GSK3) and ERK1/2 in axon regeneration failure in lesioned cortical neurons. We also investigated whether pharmacological blockage of GSK3 and ERK1/2 activities facilitates regeneration after myelin-directed inhibition in two models: i) cerebellar granule cells and ii) lesioned entorhino-hippocampal pathway in slice cultures, and whether the regenerative effects are mediated by Nogo Receptor 1 (NgR1). We demonstrate that, in contrast to ERK1/2 inhibition, the pharmacological treatment of GSK3 inhibition strongly facilitated regrowth of cerebellar granule neurons over myelin independently of NgR1. Lastly these regenerative effects were corroborated in the lesioned EHP in NgR1 -/- mutant mice. These results provide new findings for the development of new assays and strategies to enhance axon regeneration in injured cortical connections. |
Materia(s):
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-Neurones -Neurobiologia -Regeneració del sistema nerviós -Neurons -Neurobiology -Nervous system regeneration |
Derechos:
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(c) International Society for Neurochemistry, 2010
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Tipo de documento:
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Artículo Artículo - Versión presentada |
Editor:
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Wiley
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