β-RA reduces DMQ/CoQ ratio and rescues the encephalopathic phenotype in Coq9^R239X mice.

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 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 (DMQ₉) and the increase of mitochondrial bioenergetics in peripher

SUBMITTER: Hidalgo-Gutierrez A 

PROVIDER: S-EPMC6328940 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature