PMID- 35454103
OWN - NLM
STAT- MEDLINE
DCOM- 20220426
LR  - 20220716
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 12
IP  - 4
DP  - 2022 Mar 29
TI  - Curcumin and Ethanol Effects in Trembler-J Schwann Cell Culture.
LID - 10.3390/biom12040515 [doi]
LID - 515
AB  - 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.
FAU - Vazquez Alberdi, Lucia
AU  - Vazquez Alberdi L
AUID- ORCID: 0000-0002-3398-4961
AD  - Laboratorio de Biologia Celular del Sistema Nervioso Periferico, Departamento de 
      Proteinas y Acidos Nucleicos, Instituto de Investigaciones Biologicas Clemente 
      Estable, Montevideo 11600, Uruguay.
FAU - Rosso, Gonzalo
AU  - Rosso G
AUID- ORCID: 0000-0003-4847-9850
AD  - Max-Planck-Institute for the Science of Light, 91058 Erlangen, Germany.
AD  - Max-Planck-Zentrum fur Physik und Medizin, 91058 Erlangen, Germany.
AD  - Institute of Physiology II, University of Munster, 48149 Munster, Germany.
FAU - Veloz, Lucia
AU  - Veloz L
AD  - Seccion Biologia Celular, Facultad de Ciencias, Universidad de la Republica, 
      Montevideo 11400, Uruguay.
FAU - Romeo, Carlos
AU  - Romeo C
AD  - Departamento de Proteinas y Acidos Nucleicos, Instituto de Investigaciones 
      Biologicas Clemente Estable, Montevideo 11600, Uruguay.
FAU - Farias, Joaquina
AU  - Farias J
AUID- ORCID: 0000-0003-2167-9123
AD  - Espacio de Biologia Vegetal del Noreste, Centro Universitario de Tacuarembo, 
      CENUR Noreste, Universidad de la Republica, Tacuarembo 45000, Uruguay.
FAU - Di Tomaso, Maria Vittoria
AU  - Di Tomaso MV
AD  - Departamento de Genetica, Instituto de Investigaciones Biologicas Clemente 
      Estable, Montevideo 11600, Uruguay.
FAU - Calero, Miguel
AU  - Calero M
AUID- ORCID: 0000-0001-5366-3324
AD  - Unidad de Encefalopatias Espongiformes, UFIEC, CIBERNED, Instituto de Salud 
      Carlos III, 28029 Madrid, Spain.
AD  - Queen Sofia Foundation Alzheimer Center, CIEN Foundation, 28031 Madrid, Spain.
FAU - Kun, Alejandra
AU  - Kun A
AUID- ORCID: 0000-0002-7070-0171
AD  - Laboratorio de Biologia Celular del Sistema Nervioso Periferico, Departamento de 
      Proteinas y Acidos Nucleicos, Instituto de Investigaciones Biologicas Clemente 
      Estable, Montevideo 11600, Uruguay.
AD  - Seccion Bioquimica, Facultad de Ciencias, Universidad de la Republica, Montevideo 
      11400, Uruguay.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220329
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0 (Myelin Proteins)
RN  - 3K9958V90M (Ethanol)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - Animals
MH  - Cell Culture Techniques
MH  - *Charcot-Marie-Tooth Disease/drug therapy/genetics/metabolism
MH  - *Curcumin/pharmacology
MH  - Ethanol/pharmacology
MH  - Mammals/metabolism
MH  - Mice
MH  - Myelin Proteins/genetics/metabolism
PMC - PMC9025918
OTO - NOTNLM
OT  - CMT1E
OT  - Hsps
OT  - Trembler-J
OT  - autophagy
OT  - curcumin
OT  - ethanol
COIS- The authors declare no conflict of interest.
EDAT- 2022/04/24 06:00
MHDA- 2022/04/27 06:00
PMCR- 2022/03/29
CRDT- 2022/04/23 01:03
PHST- 2022/02/26 00:00 [received]
PHST- 2022/03/15 00:00 [revised]
PHST- 2022/03/17 00:00 [accepted]
PHST- 2022/04/23 01:03 [entrez]
PHST- 2022/04/24 06:00 [pubmed]
PHST- 2022/04/27 06:00 [medline]
PHST- 2022/03/29 00:00 [pmc-release]
AID - biom12040515 [pii]
AID - biomolecules-12-00515 [pii]
AID - 10.3390/biom12040515 [doi]
PST - epublish
SO  - Biomolecules. 2022 Mar 29;12(4):515. doi: 10.3390/biom12040515.