Hypocapnic hypothesis of Leigh disease.
作者： Ewa Pronicka
DOI: 10.1016/J.MEHY.2017.01.016
关键词: Endocrinology 、 Internal medicine 、 Mitochondrion 、 Chemistry 、 Hyperoxia 、 Respiratory alkalosis 、 Hyperventilation 、 Oxidative phosphorylation 、 Hypocapnia 、 Leigh disease 、 Gliosis
摘要: Leigh syndrome (LS) is a neurogenetic disorder of children caused by mutations in at least 75 genes which impair mitochondrial bioenergetics. The changes have typical localization basal ganglia and brainstem, histological picture spongiform appearance, vascular proliferation gliosis. ATP deprivation, free radicals lactate accumulation are suspected to be the causes. Hypocapnic hypothesis proposed paper questions energy deprivation as mechanism LS. We assume that primary harmful factor hypocapnia (decrease pCO2) respiratory alkalosis (increase pH) due hyperventilation, permanent or response stress. Inside mitochondria, pH signal high pH/low bicarbonate ion (HCO-3) transmitted soluble adenyl cyclase (sAC) through cAMP dependent manner. process can initiate brain lesions (necrosis, apoptosis, hypervascularity) OXPHOS deficient cells residing LS area brain. major message article it not depletion but intracellular alkalization (and/or hyperoxia?) seem cause includes suggestions concerning methodology for further research on therapeutic strategy.
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