Open Accessβ‐ RA reduces DMQ /CoQ ratio and rescues the encephalopathic phenotype in Coq9 R239X mice
Author(s) -
HidalgoGutiérrez Agustín,
BarriocanalCasado Eliana,
Bakkali Mohammed,
DíazCasado M Elena,
SánchezMaldonado Laura,
Romero Miguel,
Sayed Ramy K,
Prehn Cornelia,
Escames Germaine,
Duarte Juan,
AcuñaCastroviejo Darío,
López Luis C
Publication year - 2019
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201809466
Subject(s) - humanities , art
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 Coq9 R239X mouse model with fatal mitochondrial encephalopathy due to CoQ deficiency, we have tested the therapeutic potential of β‐resorcylic acid (β‐ RA ), a structural analog of the CoQ precursor 4‐hydroxybenzoic acid and the anti‐inflammatory salicylic acid. β‐ 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 ( DMQ 9 ) 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 β‐ RA administration were superior to those after CoQ 10 supplementation, its use in the clinic should be considered in CoQ deficiencies.