@misc{10481/53973,
year = {2018},
month = {11},
url = {http://hdl.handle.net/10481/53973},
abstract = {Coenzyme Q (CoQ) deficiency has been associated with primary
defects in the CoQ biosynthetic pathway or to secondary events. In
some cases, the exogenous CoQ supplementation has limited efficacy.
In the Coq9R239X mouse model with fatal mitochondrial
encephalopathy due to CoQ deficiency, we have tested the therapeutic
potential of b-resorcylic acid (b-RA), a structural analog of
the CoQ precursor 4-hydroxybenzoic acid and the anti-inflammatory
salicylic acid. b-RA noticeably rescued the phenotypic,
morphological, and histopathological signs of the encephalopathy,
leading to a significant increase in the survival. Those effects were
due to the decrease of the levels of demethoxyubiquinone-9
(DMQ9) and the increase of mitochondrial bioenergetics in peripheral
tissues. However, neither CoQ biosynthesis nor mitochondrial
function changed in the brain after the therapy, suggesting that
some endocrine interactions may induce the reduction of the
astrogliosis, spongiosis, and the secondary down-regulation of
astrocytes-related neuroinflammatory genes. Because the therapeutic
outcomes of b-RA administration were superior to those
after CoQ10 supplementation, its use in the clinic should be considered
in CoQ deficiencies.},
organization = {This
work was supported by grants from Ministerio de Economía y Competitividad,
Spain, and the ERDF (grant numbers SAF2013-47761-R and SAF2015-65786-R),
from the NIH (P01HD080642), and from the University of Granada (grant reference
“UNETE”, UCE-PP2017-06). A.H.-G. is a “FPU fellow” from the Ministerio
de Educación Cultura y Deporte, Spain. E.B.-C- and M.E.D.-C. were supported
by the Junta de Andalucía. L.C.L. was supported by the “Ramón y Cajal”
National Programme, Ministerio de Economía y Competitividad, Spain (RYC-
2011-07643).},
publisher = {European Molecular Biology Organization (EMBO)},
keywords = {Genetics},
keywords = {Gene Therapy & Genetic Disease},
keywords = {Pharmacology & Drug Discovery},
title = {β-RA reduces DMQ/CoQ ratio and rescues the encephalopathic phenotype in Coq9R239X mice},
doi = {10.15252/emmm.201809466},
author = {Hidalgo Gutiérrez, Agustín and Barriocanal Casado, Eliana and Bakkali, Mohammed and Díaz-Casado, Elena and Sánchez-Maldonado, Laura and Romero Pérez, Miguel and Sayed, Ramy K. A. and Prehn, Cornelia and Escames Rosa, Germaine and Duarte Pérez, Juan Manuel and Acuña Castroviejo, Darío and López García, Luis Carlos},
}