Neuroinflammation produced by heavy alcohol intake is due to loops of interactions between Toll-like 4 and TNF receptors, peroxisome proliferator-activated receptors and the central melanocortin system: A novel hypothesis and new therapeutic avenues
NEUROPHARMACOLOGY
| dc.creator | Flores-Bastías, Osvaldo | |
| dc.creator | Karahanian-Vartevanian, Eduardo Melkon | |
| dc.date | 2021-08-23T22:52:06Z | |
| dc.date | 2022-07-08T20:32:21Z | |
| dc.date | 2021-08-23T22:52:06Z | |
| dc.date | 2022-07-08T20:32:21Z | |
| dc.date | 2018 | |
| dc.date.accessioned | 2023-08-22T04:31:05Z | |
| dc.date.available | 2023-08-22T04:31:05Z | |
| dc.identifier | 1150850 | |
| dc.identifier | 1150850 | |
| dc.identifier | https://hdl.handle.net/10533/250919 | |
| dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/8319990 | |
| dc.description | Excessive alcohol intake induces an inflammatory response in the brain, via TNF alpha, TLR4 and NF-kappa B signaling pathways. It has been proposed that neuroinflammation would play a very important role in the development of alcohol addiction. In addition to stimulating the synthesis of inflammatory mediators such as IL-6, IL-1 beta and TNF alpha, NF-kappa B is capable of reducing the anti-inflammatory activity of PPAR alpha and PPAR gamma. Reciprocally, PPAR alpha, PPAR gamma and melanocortin 4 receptor (MC4R) can decrease the proinflammatory activity of NF-kappa B, establishing an interplay of inactivations between such nuclear factors and receptors. In this review, we hypothesize that one of the mechanisms by which alcohol produces neuroinflammation is through NF-kappa B-mediated decrease in PPAR alpha and PPAR gamma anti-inflammatory activities; in addition, ethanol negatively affects MC4R activity, decreasing the ability of this receptor to activate PPAR gamma. PPAR alpha, PPAR gamma and MC4R can be pharmacologically activated by synthetic ligands (fibrates, thiazolidinediones and synthetic peptides, respectively); in this context, we propose that the administration of such ligands would decrease neuroinflammation produced by alcohol intake. The advantage of this approach is that fibrates and thiazolidinediones are FDA-approved drugs that have been used for years in other clinical conditions, and now may offer a new perspective for the treatment of alcoholism. (C) 2017 Elsevier Ltd. All rights reserved. | |
| dc.description | Regular 2015 | |
| dc.description | FONDECYT | |
| dc.description | FONDECYT | |
| dc.language | eng | |
| dc.relation | handle/10533/111557 | |
| dc.relation | handle/10533/111541 | |
| dc.relation | handle/10533/108045 | |
| dc.relation | https://doi.org/10.1016/j.neuropharm.2017.11.003 | |
| dc.rights | Atribución-NoComercial-SinDerivadas 3.0 Chile | |
| dc.rights | http://creativecommons.org/licenses/by-nc-nd/3.0/cl/ | |
| dc.rights | info:eu-repo/semantics/article | |
| dc.rights | info:eu-repo/semantics/openAccess | |
| dc.title | Neuroinflammation produced by heavy alcohol intake is due to loops of interactions between Toll-like 4 and TNF receptors, peroxisome proliferator-activated receptors and the central melanocortin system: A novel hypothesis and new therapeutic avenues | |
| dc.title | NEUROPHARMACOLOGY | |
| dc.type | Articulo | |
| dc.type | info:eu-repo/semantics/publishedVersion |