Neuroprotection against cochlear synaptopathy and noise-induced hearing loss by a TrkB-FL-derived cell-penetrating peptide

[EN] Noise-induced hearing loss (NIHL) is the second leading cause of deafness globally. However, effective pharmacological treatments remain unavailable. Excitotoxicity, an early NIHL event, is a central mechanism in degeneration of cochlear synapses established between inner hair cells and spiral...

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Detalles Bibliográficos
Autores: Torres-Campos, Elena, Varela-Nieto, Isabel, Díaz-Guerra, Margarita
Tipo de recurso: conjunto de datos
Fecha de publicación:2026
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/424340
Acceso en línea:http://hdl.handle.net/10261/424340
https://doi.org/10.20350/digitalCSIC/18196
Access Level:acceso embargado
Palabra clave:Cell-penetrating peptides
Cochlear synaptopathy
Excitotoxicity
Neuroprotection
Neurotrophic system
Hearing loss
Excitotoxicidad
Neuroprotección
Péptidos penetrantes celulares
Pérdida auditiva
Sinaptopatía coclear
Sistema neurotrófico
id ES_2fd3c7c710d63ecc4e3e565d0e510630
oai_identifier_str oai:digital.csic.es:10261/424340
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Neuroprotection against cochlear synaptopathy and noise-induced hearing loss by a TrkB-FL-derived cell-penetrating peptide
title Neuroprotection against cochlear synaptopathy and noise-induced hearing loss by a TrkB-FL-derived cell-penetrating peptide
spellingShingle Neuroprotection against cochlear synaptopathy and noise-induced hearing loss by a TrkB-FL-derived cell-penetrating peptide
Torres-Campos, Elena
Cell-penetrating peptides
Cochlear synaptopathy
Excitotoxicity
Neuroprotection
Neurotrophic system
Hearing loss
Excitotoxicidad
Neuroprotección
Péptidos penetrantes celulares
Pérdida auditiva
Sinaptopatía coclear
Sistema neurotrófico
title_short Neuroprotection against cochlear synaptopathy and noise-induced hearing loss by a TrkB-FL-derived cell-penetrating peptide
title_full Neuroprotection against cochlear synaptopathy and noise-induced hearing loss by a TrkB-FL-derived cell-penetrating peptide
title_fullStr Neuroprotection against cochlear synaptopathy and noise-induced hearing loss by a TrkB-FL-derived cell-penetrating peptide
title_full_unstemmed Neuroprotection against cochlear synaptopathy and noise-induced hearing loss by a TrkB-FL-derived cell-penetrating peptide
title_sort Neuroprotection against cochlear synaptopathy and noise-induced hearing loss by a TrkB-FL-derived cell-penetrating peptide
dc.creator.none.fl_str_mv Torres-Campos, Elena
Varela-Nieto, Isabel
Díaz-Guerra, Margarita
author Torres-Campos, Elena
author_facet Torres-Campos, Elena
Varela-Nieto, Isabel
Díaz-Guerra, Margarita
author_role author
author2 Varela-Nieto, Isabel
Díaz-Guerra, Margarita
author2_role author
author
dc.contributor.none.fl_str_mv Comunidad de Madrid
Ministerio de Ciencia e Innovación (España)
Agencia Estatal de Investigación (España)
European Commission
elenatorres@iib.uam.es
i.varela.nieto@csic.es
mdiazguerra@iib.uam.es
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Cell-penetrating peptides
Cochlear synaptopathy
Excitotoxicity
Neuroprotection
Neurotrophic system
Hearing loss
Excitotoxicidad
Neuroprotección
Péptidos penetrantes celulares
Pérdida auditiva
Sinaptopatía coclear
Sistema neurotrófico
topic Cell-penetrating peptides
Cochlear synaptopathy
Excitotoxicity
Neuroprotection
Neurotrophic system
Hearing loss
Excitotoxicidad
Neuroprotección
Péptidos penetrantes celulares
Pérdida auditiva
Sinaptopatía coclear
Sistema neurotrófico
description [EN] Noise-induced hearing loss (NIHL) is the second leading cause of deafness globally. However, effective pharmacological treatments remain unavailable. Excitotoxicity, an early NIHL event, is a central mechanism in degeneration of cochlear synapses established between inner hair cells and spiral ganglion neurons. This excitotoxic damage can trigger the degradation of the neurotrophic TrkB receptor, thereby inhibiting brain-derived neurotrophic factor (BDNF) signaling and challenging neurotrophin-based therapies for hearing loss. Here, we evaluate the therapeutic potential in the inner ear of MTFL457, a cell-penetrating peptide that prevents TrkB-FL degradation during brain excitotoxicity. This peptide efficiently distributes through cochlear cells in both ex vivo (explants) and in vivo (noise-overexposed) models. In explants undergoing excitotoxicity, MTFL457 prevents TrkB-FL dysregulation, recovers downstream prosurvival signaling, and reduces neurodegeneration and cochlear synaptopathy. Furthermore, despite sexual dimorphism in noise damage susceptibility in vivo, MTFL457 preserves hearing function and synapses, demonstrating its therapeutic potential for NIHL and possibly other types of sensorineural hearing loss likewise associated with excitotoxicity.
publishDate 2026
dc.date.none.fl_str_mv 2026
2026
2026
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dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/424340
https://doi.org/10.20350/digitalCSIC/18196
url http://hdl.handle.net/10261/424340
https://doi.org/10.20350/digitalCSIC/18196
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
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info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-147347OB-I00
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application/msword
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dc.publisher.none.fl_str_mv DIGITAL.CSIC
publisher.none.fl_str_mv DIGITAL.CSIC
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
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spelling Neuroprotection against cochlear synaptopathy and noise-induced hearing loss by a TrkB-FL-derived cell-penetrating peptideTorres-Campos, ElenaVarela-Nieto, IsabelDíaz-Guerra, MargaritaCell-penetrating peptidesCochlear synaptopathyExcitotoxicityNeuroprotectionNeurotrophic systemHearing lossExcitotoxicidadNeuroprotecciónPéptidos penetrantes celularesPérdida auditivaSinaptopatía coclearSistema neurotrófico[EN] Noise-induced hearing loss (NIHL) is the second leading cause of deafness globally. However, effective pharmacological treatments remain unavailable. Excitotoxicity, an early NIHL event, is a central mechanism in degeneration of cochlear synapses established between inner hair cells and spiral ganglion neurons. This excitotoxic damage can trigger the degradation of the neurotrophic TrkB receptor, thereby inhibiting brain-derived neurotrophic factor (BDNF) signaling and challenging neurotrophin-based therapies for hearing loss. Here, we evaluate the therapeutic potential in the inner ear of MTFL457, a cell-penetrating peptide that prevents TrkB-FL degradation during brain excitotoxicity. This peptide efficiently distributes through cochlear cells in both ex vivo (explants) and in vivo (noise-overexposed) models. In explants undergoing excitotoxicity, MTFL457 prevents TrkB-FL dysregulation, recovers downstream prosurvival signaling, and reduces neurodegeneration and cochlear synaptopathy. Furthermore, despite sexual dimorphism in noise damage susceptibility in vivo, MTFL457 preserves hearing function and synapses, demonstrating its therapeutic potential for NIHL and possibly other types of sensorineural hearing loss likewise associated with excitotoxicity.[ES] La pérdida auditiva inducida por ruido (NIHL, por sus siglas en inglés) constituye la segunda causa más frecuente de sordera a nivel mundial. No obstante, en la actualidad no se dispone de tratamientos farmacológicos eficaces. La excitotoxicidad, un evento temprano en la NIHL, representa un mecanismo central en la degeneración de las sinapsis cocleares establecidas entre las células ciliadas internas y las neuronas del ganglio espiral. Este daño excitotóxico puede desencadenar la degradación del receptor neurotrófico TrkB, inhibiendo así las vías de señalización mediadas por el factor neurotrófico derivado del cerebro (BDNF) y limitando la eficacia de las terapias para la pérdida auditiva basadas en neurotrofinas. En este estudio, evaluamos el potencial terapéutico en el oído interno de MTFL457, un péptido capaz de penetrar en las células, que previene la degradación de la isoforma completa del receptor TrkB (TrkB-FL) durante procesos de excitotoxicidad cerebral. Este péptido se distribuye eficazmente en las células cocleares tanto en modelos ex vivo (explantes) como in vivo (exposición excesiva al ruido). En explantes sometidos a excitotoxicidad, MTFL457 previene la desregulación de TrkB-FL, preserva las vías de señalización prosupervivencia y reduce la neurodegeneración y la sinaptopatía coclear. Además, a pesar de la existencia de un dimorfismo sexual en la susceptibilidad al daño por ruido in vivo, MTFL457 preserva la función auditiva y la integridad sináptica, lo que pone de manifiesto su potencial terapéutico para la NIHL y, posiblemente, para otros tipos de pérdida auditiva neurosensorial igualmente asociados con procesos de excitotoxicidad.This research was funded by an Industrial Doctorate project (IND2020/BMD-17454) from Comunidad de Madrid, with the participation of Alodia Farmacéutica S.L., and by MICIU/AEI/10.13039/501100011033/FEDER, UE, as part of projects PID2022-137710OB-I00 granted to Margarita Díaz-Guerra and PID2023−147347OB-I00 granted to Isabel Varela-Nieto.Peer reviewedDIGITAL.CSICComunidad de MadridMinisterio de Ciencia e Innovación (España)Agencia Estatal de Investigación (España)European Commissionelenatorres@iib.uam.esi.varela.nieto@csic.esmdiazguerra@iib.uam.esConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202620262026info:eu-repo/semantics/datasethttp://purl.org/coar/resource_type/c_ddb1application/pdfapplication/mswordapplication/vnd.ms-excelhttp://hdl.handle.net/10261/424340https://doi.org/10.20350/digitalCSIC/18196reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#S2020/BMD-17454info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-137710OB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-147347OB-I00Síinfo:eu-repo/semantics/embargoedAccessoai:digital.csic.es:10261/4243402026-05-22T06:33:51Z
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