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Hidalgo-Gutiérrez, A.* ; Barriocanal-Casado, E.* ; Bakkali, M.* ; Díaz-Casado, M.E.* ; Sánchez-Maldonado, L.* ; Romero, M.* ; Sayed, R.K.* ; Prehn, C. ; Escames, G.* ; Duarte, J.* ; Acuña-Castroviejo, D.* ; López, L.C.*

beta-RA reduces DMQ/CoQ ratio and rescues the encephalopathic phenotype in Coq9(R239X) mice.

EMBO Mol. Med. 10:e9466 (2018)
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Open Access Gold
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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 beta-resorcylic acid (beta-RA), a structural analog of the CoQ precursor 4-hydroxybenzoic acid and the anti-inflammatory salicylic acid. beta-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 beta-RA administration were superior to those after CoQ(10) supplementation, its use in the clinic should be considered in CoQ deficiencies.
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Publication type Article: Journal article
Document type Scientific Article
Keywords 2,4‐dihydroxybenzoic Acid ; Q Synthome ; Astrogliosis ; Mitochondrial Encephalopathy ; Spongiosis; Coenzyme-q Biosynthesis; Hydrogen-sulfide; Mouse Model; 4-hydroxybenzoic Acid; Astrocyte Activation; Coq(10) Deficiency; Nephrotic Syndrome; Chemical Analogs; Q(10); Coq6
Reviewing status
Institute(s) Molecular endocrinology and metabolism (MEM)