Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0085383 (
hypocapnia
)
1,697
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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 in basal ganglia and brainstem, and typical histological picture of spongiform appearance, vascular proliferation and gliosis. ATP deprivation, free radicals and lactate accumulation are suspected to be the causes.
Hypocapnic
hypothesis proposed in the paper questions the energy deprivation as the mechanism of LS. We assume that the primary harmful factor is
hypocapnia
(decrease in pCO
2
) and respiratory alkalosis (increase in pH) due to hyperventilation, permanent or in response to stress. Inside mitochondria, the pH signal of high pH/low bicarbonate ion (HCO
-
3
) is transmitted by soluble adenyl cyclase (sAC) through cAMP dependent manner. The process can initiate brain lesions (necrosis, apoptosis, hypervascularity) in
OXPHOS
deficient cells residing at the LS area of the brain. The major message of the article is that it is not the ATP depletion but intracellular alkalization (and/or hyperoxia?) which seem to be the cause of LS. The paper includes suggestions concerning the methodology for further research on the LS mechanism and for therapeutic strategy.
...
PMID:Hypocapnic hypothesis of Leigh disease. 2835 84
