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dc.contributor.authorVázquez Alberdi, Lucia
dc.contributor.authorRosso, Gonzalo
dc.contributor.authorVelóz, Lucía
dc.contributor.authorRomeo, Carlos
dc.contributor.authorFarias, Joaquina
dc.contributor.authorDi Tomaso, María Vittoria
dc.contributor.authorCalero, Miguel 
dc.contributor.authorKun, Alejandra
dc.identifier.citationBiomolecules. 2022 Mar 29;12(4):515.es_ES
dc.description.abstractCharcot-Marie-Tooth (CMT) syndrome is the most common progressive human motor and sensory peripheral neuropathy. CMT type 1E is a demyelinating neuropathy affecting Schwann cells due to peripheral-myelin-protein-22 (PMP22) mutations, modelized by Trembler-J mice. Curcumin, a natural polyphenol compound obtained from turmeric (Curcuma longa), exhibits dose- and time-varying antitumor, antioxidant and neuroprotective properties, however, the neurotherapeutic actions of curcumin remain elusive. Here, we propose curcumin as a possible natural treatment capable of enhancing cellular detoxification mechanisms, resulting in an improvement of the neurodegenerative Trembler-J phenotype. Using a refined method for obtaining enriched Schwann cell cultures, we evaluated the neurotherapeutic action of low dose curcumin treatment on the PMP22 expression, and on the chaperones and autophagy/mammalian target of rapamycin (mTOR) pathways in Trembler-J and wild-type genotypes. In wild-type Schwann cells, the action of curcumin resulted in strong stimulation of the chaperone and macroautophagy pathway, whereas the modulation of ribophagy showed a mild effect. However, despite the promising neuroprotective effects for the treatment of neurological diseases, we demonstrate that the action of curcumin in Trembler-J Schwann cells could be impaired due to the irreversible impact of ethanol used as a common curcumin vehicle necessary for administration. These results contribute to expanding our still limited understanding of PMP22 biology in neurobiology and expose the intrinsic lability of the neurodegenerative Trembler-J genotype. Furthermore, they unravel interesting physiological mechanisms of cellular resilience relevant to the pharmacological treatment of the neurodegenerative Tremble J phenotype with curcumin and ethanol. We conclude that the analysis of the effects of the vehicle itself is an essential and inescapable step to comprehensibly assess the effects and full potential of curcumin treatment for therapeutic purposes.es_ES
dc.description.sponsorshipThis research was funded by the Comisión Sectorial de Investigación Científica de la Universidad de la República (CSIC I+D, 2013), Agencia Nacional de Investigación e Innovación (ANII, FCE_1_2019_1_155539) and Programa de Desarrollo de Ciencias Básicas (PEDECIBA, CCA-Bio/Res. 6.1-2/4/2019). This work was also supported by a grant PID2019-110401RB-100 from the Spanish, Ministry of Science and Innovation and the Spanish CIBERNED network (M.C.).es_ES
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI) es_ES
dc.subject.meshCharcot-Marie-Tooth Disease es_ES
dc.subject.meshCurcumin es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshCell Culture Techniques es_ES
dc.subject.meshEthanol es_ES
dc.subject.meshMammals es_ES
dc.subject.meshMice es_ES
dc.subject.meshMyelin Proteins es_ES
dc.titleCurcumin and Ethanol Effects in Trembler-J Schwann Cell Culturees_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderMinisterio de Ciencia e Innovación (España) es_ES
dc.contributor.funderCentro de Investigación Biomédica en Red - CIBERNED (Enfermedades Neurodegenerativas) 
dc.contributor.funderUniversity of the Republic (Uruguay) 
dc.contributor.funderAgencia Nacional de Investigación e Innovación (Uruguay) 
dc.repisalud.centroISCIII::Unidad Funcional de Investigación de Enfermedades Crónicas (UFIEC)es_ES
dc.rights.accessRightsopen accesses_ES

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