2026-07-21T15:10:28Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/148132025-06-13T07:47:43Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19617
Repisalud
author
Vázquez Alberdi, Lucia
author
Rosso, Gonzalo
author
Velóz, Lucía
author
Romeo, Carlos
author
Farias, Joaquina
author
Di Tomaso, María Vittoria
author
Calero, Miguel
author
Kun, Alejandra
funder
Ministerio de Ciencia e Innovación (España)
funder
Centro de Investigación Biomédica en Red - CIBERNED (Enfermedades Neurodegenerativas)
funder
University of the Republic (Uruguay)
funder
Agencia Nacional de Investigación e Innovación (Uruguay)
2022-08-03T07:47:30Z
2022-08-03T07:47:30Z
2022-03-29
Biomolecules. 2022 Mar 29;12(4):515.
10.3390/biom12040515
2218-273X
Biomolecules
35454103
http://hdl.handle.net/20.500.12105/14813
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.
eng
CMT1E
Hsps
Trembler-J
Autophagy
Curcumin
Ethanol
Curcumin and Ethanol Effects in Trembler-J Schwann Cell Culture
research article
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CurcuminAndEthanolEffects_2022.pdf.txt
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