Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: EC:1.3.5.1 (
succinate dehydrogenase
)
8,177
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Previous studies in primates have shown that chronic systemic administration of the
succinate dehydrogenase
(
SDH
) inhibitor, 3-nitropropionic acid (3NP), replicates most of the motor, cognitive, and histopathological features of Huntington's disease. In the present study, serial 1H-NMR spectroscopy (1H-MRS) assessment of striatal and occipital cortex concentrations of
N-acetylaspartate
, phosphocreatine/creatine, choline, and lactate, were obtained every 2-weeks during the entire course of a chronic 3NP treatment in baboons. A region-selective increase in lactate was detected in the striatum of the 3NP-treated animals, either immediately before or in conjunction with a lesion in the dorsolateral putamen detected by T2-MR imaging. Absolute 1H-MRS quantitation demonstrated a progressive and region-specific decrease in striatal
N-acetylaspartate
, creatine, and choline, occuring as early as 3 weeks before the first detection of lactate. These results demonstrate that 1H-MRS can be used to monitor early stages of brain metabolic impairment. In addition, given that 3NP-induced
SDH
inhibition following systemic injection similarly affects all brain regions, the striatal selective decreases in
N-acetylaspartate
or creatine concentrations are not simply related to the level of mitochondrial impairment but to a preferential vulnerability of the striatum to 3NP-induced toxicity.
...
PMID:Serial 1H-NMR spectroscopy study of metabolic impairment in primates chronically treated with the succinate dehydrogenase inhibitor 3-nitropropionic acid. 1044 53
To investigate the mechanisms of neuronal death in neurodegeneration, in vivo localized proton magnetic resonance spectroscopy ((1)H-MRS) and diffusion-weighted MRI (DWI) were used to evaluate temporal changes in rat striata after administration of 3-nitropropionic acid. It was found that
N-acetylaspartate
(
NAA
) reduction, with nearly simultaneous evidence of striatal lesions in DWI, was preceded by a significant and progressive increase of acetate. Shortly before the
NAA
levels decreased to the lowest point, acetate levels peaked and began to gradually decline toward the control levels. These results suggest that acetate increase may arise from fatty acid degradation, inhibition of
succinate dehydrogenase
and possible
NAA
hydrolysis. The elevated acetate may provide a source of acetyl group for membrane repair during excitotoxic brain injury. Magn Reson Med 44:29-34, 2000.
...
PMID:Temporal changes of cerebral metabolites and striatal lesions in acute 3-nitropropionic acid intoxication in the rat. 1089 18
In childhood mitochondrial encephalopathies the common MRI features are bilateral symmetric abnormalities in basal nuclei and brainstem. The presence of diffuse white matter abnormality has been described only in a few cases. Among a series of 110 children with mitochondrial encephalopathies, 8 patients with MR imaging consistent with a leukoencephalopathy were retrospectively evaluated. Diagnosis was based on the recognition of the biochemical defect in muscle homogenate. H-MR spectroscopic imaging was performed in six of them. Biochemical analysis demonstrated a defect of respiratory chain complexes in six patients: complex I in two cases,
complex II
in two, complex IV in one, multiple complexes defect in one. Pyruvate dehydrogenase deficiency was demonstrated in two patients. MRI showed severe involvement of the brain white matter without significant basal nuclei or brainstem abnormalities. Two patients developed large cystic areas since onset; in two others progressive vacuolisation of affected white matter was seen later in the course of the disease. One patient with pyruvate dehydrogenase deficiency also presented with a diffuse cortical polymicrogyria. H-MR spectroscopic imaging showed a decrease of
N-acetylaspartate
, choline and creatine with lactate accumulation in five patients, and was normal in one. These findings suggest that mitochondrial disorders should be included in the differential diagnosis of white matter disorders.
...
PMID:Cerebral white matter involvement in children with mitochondrial encephalopathies. 1207 88
The effects of normothermia and delayed hypothermia on the levels of
N-acetylaspartate
(
NAA
), reduced glutathione (GSH) and the activities of mitochondrial complex I, II-III, IV and citrate synthase were measured in brain homogenates obtained from anaesthetized neonatal pigs following transient in vivo hypoxia-ischaemia. In the normothermic animals there was a significant decrease in complex I activity and in the levels of GSH and
NAA
when compared to the controls. Delayed hypothermia preserved
NAA
and GSH at control levels and enhanced the rate of
complex II
-III activity. There was correlation (R = 0.79) between GSH and
NAA
levels when data from all three experimental groups were analyzed. Citrate synthase activity was not significantly different in the three groups, indicating maintenance of mitochondrial integrity. These data suggest that delayed hypothermia affords protection of integrated mitochondrial function in the neonatal brain following transient hypoxia-ischaemia.
...
PMID:Delayed hypothermia prevents decreases in N-acetylaspartate and reduced glutathione in the cerebral cortex of the neonatal pig following transient hypoxia-ischaemia. 1251 11
Huntington disease (HD) is a hereditary brain disease. Although the causative gene has been found, the exact mechanisms of the pathogenesis are still unknown. Recent investigations point to metabolic and energetic dysfunctions in HD neurons. Both univariate and multivariate analyses were used to compare proton nuclear magnetic resonance spectra of serum and cerebrospinal fluid (CSF) taken from presymptomatic HD transgenic rats and their wild-type littermates.
N-acetylaspartate
(
NAA
), was found to be significantly decreased in the serum of HD rats compared to wild-type littermates. Moreover, in the serum their levels of glutamine, succinic acid, glucose and lactate are significantly increased as well. An increased concentration of lactate and glucose is also found in CSF. There is a 1:1 stoichiometry coupling glucose utilization and glutamate cycling. The observed increase in the glutamine concentration, which indicates a shutdown in the neuronal-glial glutamate-glutamine cycling, results therefore in an increased glucose concentration. The elevated succinic acid concentration might be due to an inhibition of
succinate dehydrogenase
, an enzyme linked to the mitochondrial respiratory chain and TCA cycle. Moreover, reduced levels of
NAA
may reflect an impairment of mitochondrial energy production. In addition, the observed difference in lactate supports a deficiency of oxidative energy metabolism in rats transgenic for HD as well. The observed metabolic alterations seem to be more profound in serum than in CSF in presymptomatic rats. All findings suggest that even in presymptomatic rats, a defect in energy metabolism is already apparent. These results support the hypothesis of mitochondrial energy dysfunction in HD.
...
PMID:(1)H NMR based metabolomics of CSF and blood serum: a metabolic profile for a transgenic rat model of Huntington disease. 2186 51
