{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:24:12Z","timestamp":1772252652676,"version":"3.50.1"},"reference-count":102,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T00:00:00Z","timestamp":1648512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Comisi\u00f3n Sectorial de Investigaci\u00f3n Cient\u00edfica de la Universidad de la Rep\u00fablica","award":["CSIC I+D, 2013"],"award-info":[{"award-number":["CSIC I+D, 2013"]}]},{"DOI":"10.13039\/100008725","name":"Agencia Nacional de Investigaci\u00f3n e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["ANII, FCE_1_2019_1_155539"],"award-info":[{"award-number":["ANII, FCE_1_2019_1_155539"]}],"id":[{"id":"10.13039\/100008725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Programa de Desarrollo de Ciencias B\u00e1sicas","award":["PEDECIBA, CCA-Bio\/ Res. 6.1-2\/4\/2019"],"award-info":[{"award-number":["PEDECIBA, CCA-Bio\/ Res. 6.1-2\/4\/2019"]}]},{"name":"the Spanish, Ministry of Science and Innovation","award":["PID2019-110401RB-100"],"award-info":[{"award-number":["PID2019-110401RB-100"]}]},{"name":"the Spanish CIBERNED network","award":["M.C."],"award-info":[{"award-number":["M.C."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Charcot-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.<\/jats:p>","DOI":"10.3390\/biom12040515","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T21:40:14Z","timestamp":1648590014000},"page":"515","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Curcumin and Ethanol Effects in Trembler-J Schwann Cell Culture"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3398-4961","authenticated-orcid":false,"given":"Lucia","family":"V\u00e1zquez Alberdi","sequence":"first","affiliation":[{"name":"Laboratorio de Biolog\u00eda Celular del Sistema Nervioso Perif\u00e9rico, Departamento de Prote\u00ednas y \u00c1cidos Nucleicos, Instituto de Investigaciones Biol\u00f3gicas Clemente Estable, Montevideo 11600, Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4847-9850","authenticated-orcid":false,"given":"Gonzalo","family":"Rosso","sequence":"additional","affiliation":[{"name":"Max-Planck-Institute for the Science of Light, 91058 Erlangen, Germany"},{"name":"Max-Planck-Zentrum f\u00fcr Physik und Medizin, 91058 Erlangen, Germany"},{"name":"Institute of Physiology II, University of M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc\u00eda","family":"Vel\u00f3z","sequence":"additional","affiliation":[{"name":"Secci\u00f3n Biolog\u00eda Celular, Facultad de Ciencias, Universidad de la Rep\u00fablica, Montevideo 11400, Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Romeo","sequence":"additional","affiliation":[{"name":"Departamento de Prote\u00ednas y \u00c1cidos Nucleicos, Instituto de Investigaciones Biol\u00f3gicas Clemente Estable, Montevideo 11600, Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2167-9123","authenticated-orcid":false,"given":"Joaquina","family":"Farias","sequence":"additional","affiliation":[{"name":"Espacio de Biolog\u00eda Vegetal del Noreste, Centro Universitario de Tacuaremb\u00f3, CENUR Noreste, Universidad de la Rep\u00fablica, Tacuaremb\u00f3 45000, Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Vittoria","family":"Di Tomaso","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica, Instituto de Investigaciones Biol\u00f3gicas Clemente Estable, Montevideo 11600, Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5366-3324","authenticated-orcid":false,"given":"Miguel","family":"Calero","sequence":"additional","affiliation":[{"name":"Unidad de Encefalopat\u00edas Espongiformes, UFIEC, CIBERNED, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Queen Sofia Foundation Alzheimer Center, CIEN Foundation, 28031 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7070-0171","authenticated-orcid":false,"given":"Alejandra","family":"Kun","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda Celular del Sistema Nervioso Perif\u00e9rico, Departamento de Prote\u00ednas y \u00c1cidos Nucleicos, Instituto de Investigaciones Biol\u00f3gicas Clemente Estable, Montevideo 11600, Uruguay"},{"name":"Secci\u00f3n Bioqu\u00edmica, Facultad de Ciencias, Universidad de la Rep\u00fablica, Montevideo 11400, Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/j.1399-0004.1974.tb00638.x","article-title":"Genetic and clinical aspects of Charcot-Marie-Tooth\u2019s disease","volume":"6","author":"Skre","year":"1974","journal-title":"Clin. 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