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

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytidine 5'-diphosphocholine, CDP-choline or citicoline, is an essential intermediate in the biosynthetic pathway of the structural phospholipids of cell membranes, especially in that of phosphatidylcholine. Upon oral or parenteral administration, CDP-choline releases its two principle components, cytidine and choline. When administered orally, it is absorbed almost completely, and its bioavailability is approximately the same as when administered intravenously. Once absorbed, the cytidine and choline disperse widely throughout the organism, cross the blood-brain barrier and reach the central nervous system (CNS), where they are incorporated into the phospholipid fraction of the membrane and microsomes. CDP-choline activates the biosynthesis of structural phospholipids in the neuronal membranes, increases cerebral metabolism and acts on the levels of various neurotransmitters. Thus, it has been experimentally proven that CDP-choline increases noradrenaline and dopamine levels in the CNS. Due to these pharmacological activities, CDP-choline has a neuroprotective effect in situations of hypoxia and ischemia, as well as improved learning and memory performance in animal models of brain aging. Furthermore, it has been demonstrated that CDP-choline restores the activity of mitochondrial ATPase and of membranal Na+/K+ ATPase, inhibits the activation of phospholipase A2 and accelerates the reabsorption of cerebral edema in various experimental models. CDP-choline is a safe drug, as toxicological tests have shown; it has no serious effects on the cholinergic system and it is perfectly tolerated. These pharmacological characteristics, combined with CDP-choline's mechanisms of action, suggest that this drug may be suitable for the treatment of cerebral vascular disease, head trauma of varying severity and cognitive disorders of diverse etiology. In studies carried out on the treatment of patients with head trauma, CDP-choline accelerated the recovery from post-traumatic coma and the recuperation of walking ability, achieved a better final functional result and reduced the hospital stay of these patients, in addition to improving the cognitive and memory disturbances which are observed after a head trauma of lesser severity and which constitute the disorder known as postconcussion syndrome. In the treatment of patients with acute cerebral vascular disease of the ischemic type, CDP-choline accelerated the recovery of consciousness and motor deficit, attaining a better final result and facilitating the rehabilitation of these patients. The other important use for CDP-choline is in the treatment of senile cognitive impairment, which is secondary to degenerative diseases (e.g., Alzheimer's disease) and to chronic cerebral vascular disease. In patients with chronic cerebral ischemia, CDP-choline improves scores on cognitive evaluation scales, while in patients with senile dementia of the Alzheimer's type, it slows the disease's evolution. Beneficial neuroendocrine, neuroimmunomodulatory and neurophysiological effects have been described. CDP-choline has also been shown to be effective as co-therapy for Parkinson's disease. No serious side effects have been found in any of the groups of patients treated with CDP-choline, which demonstrates the safety of the treatment.
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PMID:CDP-choline: pharmacological and clinical review. 870 78

The isoprenoid pathway was assessed in 15 patients with chronic fatigue syndrome. The pathway was also assessed in individuals with differing hemispheric dominance to assess whether hemispheric dominance had any correlation with these disease states. The isoprenoid metabolites--digoxin, dolichol, and ubiquinone--RBC membrane Na+-K+ ATPase activity, serum magnesium and tyrosine/tryptophan catabolic patterns were assessed. The free-radical metabolism, glycoconjugate metabolism, and RBC membrane composition was also assessed. Membrane Na+-K+ ATPase activity and serum magnesium levels were decreased while HMG CoA reductase activity and serum digoxin levels were increased in myalgic encephalomyelitis (ME). There were increased levels of tryptophan catabolites--nicotine, strychnine, quinolinic acid, and serotonin--and decreased levels of tyrosine catabolites--dopamine, noradrenaline, and morphine in ME. There was an increase in dolichol levels, carbohydrate residues of glycoproteins, glycolipids, total/individual GAG fractions, and lysosomal enzymes in ME. Reduced levels of ubiquinone, reduced glutathione, and free-radical scavenging enzymes, as well as increased lipid peroxidation products and nitric oxide, were noticed in ME. The biochemical patterns in ME correlated with those obtained in right hemi spheric chemical dominance. The role of hypothalamic digoxin and neurotransmitter induced immune activation, altered glycoconjugate metabolism, and resultant defective viral antigen presentation, NMDA excitotoxicity and cognitive dysfunction, and mitochondrial dysfunction related myalgia in the pathogenesis of ME is stressed. ME occurs in individuals with right hemispheric chemical dominance.
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PMID:Hypothalamic digoxin, cerebral chemical dominance and myalgic encephalomyelitis. 1274 27

With regards to the applications of three Chinese herbs poria, rhizoma atractylodis macrocephalae, and radix angelicae sinensis to vascular dementia (VD), the work was performed to assess the nootropic action and explore neuroprotective mechanisms of three herbs combinations (FBD) on mice injured by cerebral repetitive ischemia-reperfusion (IR). Aqueous extracts from FBD (115-460 mg/kg) administered p.o. significantly improved cognitive function through elongating latency and reducing number of errors in step-through test. Aqueous extracts from FBD inhibited lipid peroxidation (LPO), elevated activity in (Na+)-(K+)-ATPase and (Ca2+)-ATPase, reduced the production of nitric oxide (NO) in cortical tissue after IR, and artificial cerebrospinal fluid (ACSF) containing aqueous extracts from FBD (ACSF-FBD) (0.01-10 mg/L) protected also primary cortical cortex neurons (PCCN) from hypoxic and excitotoxic insult induced by sodium dithionite (1 mM) and monosodium glutamate (MSG) (0.5 mM) in vitro. Multiple anti-IR properties contributed probably FBD to ameliorate cognitive dysfunction shown in this murine model for VD.
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PMID:Protective effects of FBD--an experimental Chinese traditional medicinal formula on memory dysfunction in mice induced by cerebral ischemia-reperfusion. 1574 Aug 83

Wilson's disease and Menkes disease are inherited genetic disorders of copper metabolism. Each disease results from the absence or dysfunction of homologous copper-transporting ATPases present in the trans-Golgi network of cells. The Wilson ATPase transports copper into the hepatocyte secretory pathway for incorporation into ceruloplasmin and excretion into the bile. Thus, patients with Wilson's disease of the autosomal recessive trait present with signs and symptoms arising from impaired biliary copper excretion. The Menkes ATPase transports copper across the placenta, gastrointestinal tract, and blood-brain barrier, and the clinical features of this X-linked disease arise from copper deficiency. Despite striking differences in the clinical presentation of these two diseases, the respective ATPases function in precisely the same fashion within the cell. The different clinical features of each disease are the results of the tissue specific expression of these ATPases. In Wilson's disease, impaired biliary copper excretion leads to accumulation of this metal in the liver. When the capacity for hepatic storage is exceeded, cell death ensues, with copper release into the plasma resulting in hemolysis and deposition of copper in extrahepatic tissues. Affected patients usually present in the first or second decade of life with chronic hepatitis and cirrhosis or acute liver failure. Copper accumulation in the cornea results in Kayser-Fleischer rings. Neuropsychiatric symptoms are more common in adults and include dystonia, tremor, personality changes, and cognitive impairment as a results of copper accumulation in the basal ganglia and other brain regions. The diagnosis of Wilson's disease is confirmed by decreased serum ceruloplasmin, increased urinary copper, and elevated hepatic copper concentration. A large number of different mutations occur in the genes of patients with Wilson disease. Copper chelation drugs and zinc are effective in most cases. New treatment guidelines now advise physicians to start patients on zinc.
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PMID:[Genetic disorders of copper transport--diagnosis and new treatment for the patients of Wilson's disease]. 1577 21

Neurodegenerative disorders such as Parkinson and Alzheimer disease cause motor and cognitive dysfunction and belong to a heterogeneous group of common and disabling disorders. Although the complex molecular pathophysiology of neurodegeneration is largely unknown, major advances have been achieved by elucidating the genetic defects underlying mendelian forms of these diseases. This has led to the discovery of common pathophysiological pathways such as enhanced oxidative stress, protein misfolding and aggregation and dysfunction of the ubiquitin-proteasome system. Here, we describe loss-of-function mutations in a previously uncharacterized, predominantly neuronal P-type ATPase gene, ATP13A2, underlying an autosomal recessive form of early-onset parkinsonism with pyramidal degeneration and dementia (PARK9, Kufor-Rakeb syndrome). Whereas the wild-type protein was located in the lysosome of transiently transfected cells, the unstable truncated mutants were retained in the endoplasmic reticulum and degraded by the proteasome. Our findings link a class of proteins with unknown function and substrate specificity to the protein networks implicated in neurodegeneration and parkinsonism.
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PMID:Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. 1696 63

The neuroprotective effects of catalpol, an iridoid glycoside isolated from the fresh Rehmannia roots, on the senescent mice induced by D-galactose were assessed. The mice subcutaneously injected with catalpol (5 or 10 mg/kg, 2 weeks, from fifth week) showed significantly improved learning and memory ability in Morris water maze test compared with d-galactose treated mice (150 mg/kg, 6 weeks). We further investigated the mechanism involved in the neuroprotective effects of catalpol on the mice brain tissue. The results showed that catalpol increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), decreased the malondialdehyde (MDA) level, elevated the activities of Na+ -K+ ATPase and Ca2+ -Mg2+ ATPase on the cerebral cortex and hippocampus of d-galactose treated mouse. All the data suggested that catalpol had the potential to be a useful cognitive impairment treatment, and its beneficial effects may be partly mediated via enhancing endogenous antioxidant enzymatic activities and inhibiting free radical generation.
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PMID:Catalpol ameliorates cognition deficits and attenuates oxidative damage in the brain of senescent mice induced by D-galactose. 1769 78

Traumatic brain injury (TBI) is a devastating disease that commonly causes persistent mental disturbances and cognitive deficits. Although studies indicate that oxidative stress and functional deficits occurring after TBI are interrelated events, the knowledge of the mechanisms underlying the development of such cognitive deficits has been limited. Thus, in the present study, we investigated the effect of fluid percussion brain injury (FPI) on a spatial learning task and levels of oxidative stress markers, namely, protein carbonylation and thiobarbituric acid-reactive substances (TBARS) and Na+,K+-ATPase activity 1 or 3 months after FPI in rats. Statistical analysis revealed that FPI increased the scape latency and mean number of error in Barnes maze test 1 and 3 months after FPI. We also found that protein carbonylation and TBARS content increased in the parietal cortex 1 and 3 months after FPI. In addition, 3 months after FPI, protein carbonylation levels increased both in ipsilateral and contralateral cortices of FPI animals. Indeed, statistical analysis revealed a decrease in Na+,K+-ATPase activity in the cerebral cortex of 1 month FPI animals. Furthermore, the decrease in enzyme activity found 3 months was larger, when compared with 1 month after FPI. These results suggest that cognitive impairment following TBI may result, at least in part, from increase of two oxidative stress markers, protein carbonylation and TBARS that occurs concomitantly to a decrease in Na+,K+-ATPase activity.
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PMID:Na+,K+-ATPase activity impairment after experimental traumatic brain injury: relationship to spatial learning deficits and oxidative stress. 1857 45

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in multiple cognitive domains. Its pathological hallmarks include senile plaques and neurofibrillary tangles. Mild cognitive impairment (MCI) is the earliest detectable stage of AD with limited symptomology and no dementia. The yearly conversion rate of patients from MCI to AD is 10-15%, although conversion back to normal is possible in a small percentage. Early diagnosis of AD is important in an attempt to intervene or slow the advancement of the disease. Early AD (EAD) is a stage following MCI and characterized by full-blown dementia; however, information involving EAD is limited. Oxidative stress is well-established in MCI and AD, including protein oxidation. Protein nitration also is an important oxidative modification observed in MCI and AD, and proteomic analysis from our laboratory identified nitrated proteins in both MCI and AD. Therefore, in the current study, a proteomics approach was used to identify nitrated brain proteins in the inferior parietal lobule from four subjects with EAD. Eight proteins were found to be significantly nitrated in EAD: peroxiredoxin 2, triose phosphate isomerase, glutamate dehydrogenase, neuropolypeptide h3, phosphoglycerate mutase1, H(+)- transporting ATPase, alpha-enolase and fructose-1,6-bisphosphate aldolase. Many of these proteins are also nitrated in MCI and late-stage AD, making this study the first to our knowledge to link nitrated proteins in all stages of AD. These results are discussed in terms of potential involvement in the progression of this dementing disorder.
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PMID:Proteomic identification of nitrated brain proteins in early Alzheimer's disease inferior parietal lobule. 1875 37

In the present study, we examined the supplementation of paeonol extracted from Moutan cortex of Paeonia suffruticosa Andrews (MC) or the root of Paeonia lactiflora Pall (PL) on reducing oxidative stress, cognitive impairment and neurotoxicity in d-galactose (D-gal)-induced aging mice. The ICR mice were subcutaneously injected with D-gal (50 mg/(kg day)) for 60 days and administered with paeonol (50, 100 mg/(kg day)) simultaneously. The results showed that paeonol significantly improved the learning and memory ability in Morris water maze test and step-down passive avoidance test in D-gal-treated mice. Further investigation showed that the effect of paeonol on improvement of cognitive deficit was related to its ability to inhibit the biochemical changes in brains of D-gal-treated mice. Paeonol increased acetylcholine (Ach) and glutathione (GSH) levels, restored superoxide dismutase (SOD) and Na(+), K(+)-adenosine triphosphatase (Na(+), K(+)-ATPase) activities, but decreased cholinesterase AChe activity and malondialdehyde (MDA) level in D-gal-treated mice. Furthermore, paeonol ameliorated neuronal damage in both hippocampus and temporal cortex in D-gal-treated mice. These results suggest that paeonol possesses anti-aging efficacy and may have potential in treatment of neurodegenerative diseases.
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PMID:Paeonol attenuates neurotoxicity and ameliorates cognitive impairment induced by d-galactose in ICR mice. 1900 42

Early Alzheimer's disease (EAD) is the intermediary stage between mild cognitive impairment (MCI) and late-stage Alzheimer's disease (AD). The symptoms of EAD mirror the disease advancement between the two phases. Dementia, memory deficits, and cognitive decline are more pronounced as the disease progresses. Oxidative stress in brain is reported in MCI and AD, including lipid peroxidation indexed by protein-bound 4-hydroxy-2-nonenal (HNE). There are limited data regarding the proteomics analysis of brain from subjects with EAD and even less concerning the possible relationship of EAD HNE-modified brain proteins with HNE-modified proteins in MCI and AD. Proteomics was utilized to investigate excessively HNE-bound brain proteins in EAD compared to those in control. These new results provide potentially valuable insight into connecting HNE-bound brain proteins in EAD to those previously identified in MCI and AD, since EAD is a transitional stage between MCI and late-stage AD. In total, six proteins were found to be excessively covalently bound by HNE in EAD inferior parietal lobule (IPL) compared to age-related control brain. These proteins play roles in antioxidant defense (manganese superoxide dismutase), neuronal communication and neurite outgrowth (dihydropyriminidase-related protein 2), and energy metabolism (alpha-enolase, malate dehydrogenase, triosephosphate isomerase, and F1 ATPase, alpha subunit). This study shows that there is an overlap of brain proteins in EAD with previously identified oxidatively modified proteins in MCI and late-stage AD. The results are consistent with the hypothesis that oxidative stress, in particular lipid peroxidation, is an early event in the progression of AD, and is the first to identify in EAD identical brain proteins previously identified as HNE-modified in MCI and late-state AD.
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PMID:Proteomic identification of HNE-bound proteins in early Alzheimer disease: Insights into the role of lipid peroxidation in the progression of AD. 1937 91


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