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Campo DC | Valor | Lengua/Idioma |
---|---|---|
dc.contributor.author | Marcotti, Aida | - |
dc.contributor.author | Fernández Trillo, Jorge | - |
dc.contributor.author | González, Alejandro | - |
dc.contributor.author | Vizcaíno Escoto, Marta | - |
dc.contributor.author | Ros Arlanzón, Pablo | - |
dc.contributor.author | Romero, Luz | - |
dc.contributor.author | Vela, José Miguel | - |
dc.contributor.author | Gomis García, Ana María | - |
dc.contributor.author | Viana de la Iglesia, Félix | - |
dc.contributor.author | De la Peña García, Elvira | - |
dc.contributor.other | Departamentos de la UMH::Fisiología | es_ES |
dc.contributor.other | Instituto de Neurociencias | es_ES |
dc.date.accessioned | 2024-01-26T10:25:42Z | - |
dc.date.available | 2024-01-26T10:25:42Z | - |
dc.date.created | 2023-02-13 | - |
dc.identifier.citation | Brain 2023 Feb 13;146(2):475-491 | es_ES |
dc.identifier.issn | 1460-2156 (Electronic) | - |
dc.identifier.uri | https://hdl.handle.net/11000/30712 | - |
dc.description.abstract | Chemotherapy-induced peripheral neuropathy is a frequent, disabling side effect of anticancer drugs. Oxaliplatin, a platinum compound used in the treatment of advanced colorectal cancer, often leads to a form of chemotherapy-induced peripheral neuropathy characterized by mechanical and cold hypersensitivity. Current therapies for chemotherapy-induced peripheral neuropathy are ineffective, often leading to the cessation of treatment. Transient receptor potential ankyrin 1 (TRPA1) is a polymodal, non-selective cation-permeable channel expressed in nociceptors, activated by physical stimuli and cellular stress products. TRPA1 has been linked to the establishment of chemotherapy-induced peripheral neuropathy and other painful neuropathic conditions. Sigma-1 receptor is an endoplasmic reticulum chaperone known to modulate the function of many ion channels and receptors. Sigma-1 receptor antagonist, a highly selective antagonist of Sigma-1 receptor, has shown effectiveness in a phase II clinical trial for oxaliplatin chemotherapy-induced peripheral neuropathy. However, the mechanisms involved in the beneficial effects of Sigma-1 receptor antagonist are little understood. We combined biochemical and biophysical (i.e. intermolecular Förster resonance energy transfer) techniques to demonstrate the interaction between Sigma-1 receptor and human TRPA1. Pharmacological antagonism of Sigma-1R impaired the formation of this molecular complex and the trafficking of functional TRPA1 to the plasma membrane. Using patch-clamp electrophysiological recordings we found that antagonists of Sigma-1 receptor, including Sigma-1 receptor antagonist, exert a marked inhibition on plasma membrane expression and function of human TRPA1 channels. In TRPA1-expressing mouse sensory neurons, Sigma-1 receptor antagonists reduced inward currents and the firing of actions potentials in response to TRPA1 agonists. Finally, in a mouse experimental model of oxaliplatin neuropathy, systemic treatment with a Sigma-1 receptor antagonists prevented the development of painful symptoms by a mechanism involving TRPA1. In summary, the modulation of TRPA1 channels by Sigma-1 receptor antagonists suggests a new strategy for the prevention and treatment of chemotherapy-induced peripheral neuropathy and could inform the development of novel therapeutics for neuropathic pain. | es_ES |
dc.format | application/pdf | es_ES |
dc.format.extent | 17 | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Oxford University Press [University Publisher] | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | cold allodynia | es_ES |
dc.subject | neuropathic pain | es_ES |
dc.subject | TRPA1 | es_ES |
dc.subject | Sigma-1 receptor | es_ES |
dc.subject | chemotherapy | es_ES |
dc.title | TRPA1 modulation by Sigma-1 receptor prevents oxaliplatin-induced painful peripheral neuropathy | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.relation.publisherversion | https://doi.org/10.1093/brain/awac273 | es_ES |
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