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:3.1.1.8 (cholinesterase)
12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical trials and independent reviews support the use of cholinesterase inhibitors for treating the symptoms of patients with mild to moderate Alzheimer's disease (AD). Before initiating cholinesterase inhibitor therapy, patients should be thoroughly assessed, and the diagnosis confirmed, preferably by a specialist. Compliance with cholinesterase inhibitor therapy should be monitored and the response (in global, cognitive, functional and behavioural domains) reassessed after 2-3 months of treatment. Vitamin E may be protective against AD, and therapy with 1000 IU twice daily may be considered. There is insufficient evidence to support the use of other antioxidant agents, anti-inflammatory agents, monoamine oxidase B inhibitors, folate/homocysteine or antihypertensive drugs in patients with AD, or hormone replacement therapy in affected women.
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PMID:Pharmacological treatment of cognitive deficits in Alzheimer's disease. 1199 69

In the present work we investigated the in vitro effects of homocysteine (Hcy) and methionine (Met), metabolites accumulated in homocystinuria, on butyrylcholinesterase (BuChE) activity in rat serum. We also studied the kinetics of the inhibition of BuChE activity caused by Hcy. For determination of BuChE we used serum of 60-day-old Wistar rats, which was incubated in the absence (control) or presence of Hcy (0.01-0.5 mM) or Met (0.2-2.0 mM). The kinetics of the interaction of Hcy and BuChE was determined using the Lineweaver-Burk double reciprocal plot. Results showed that serum BuChE activity was not altered by Met, but it was significantly inhibited (37%) by 500 microM Hcy, a concentration similar to those found in blood of homocystinuric patients. The apparent Km values, in the absence and presence of 500 microM of Hcy, were 0.034 and 0.142 mM, respectively, and V(max) of BuChE for acetylcholine (ACh) as substrate was 1.25 micromol ACSCh/h/mg of protein. The Ki value obtained was 120 microM, and the inhibition was of the competitive type, suggesting a common binding site for Hcy and ACh. It is proposed that inhibition of cholinesterase activity may be one of the mechanisms involved in the neurological dysfunction observed in homocystinuria.
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PMID:Homocysteine inhibits butyrylcholinesterase activity in rat serum. 1456 69

Homocystinuria is an inborn error of sulphur amino acid metabolism, resulting in accumulation of tissue homocysteine. This disease is characterized predominantly by vascular and nervous system dysfunction. In the present study we investigated the in vitro effects of homocysteine, the main metabolite accumulated in homocystinuria, on platelet Na+,K+-ATPase and serum butyrylcholinesterase (BuChE) activities of young rats. Platelet and serum of 29-day-old Wistar rats were incubated in the absence (control) or presence of homocysteine (0.01-0.5 mM). Results showed that Na+,K+-ATPase and BuChE activities were significantly inhibited by homocysteine. It is proposed that inhibition of Na+,K+-ATPase and BuChE activities might be one useful peripheral marker for the neurotoxic effects of homocysteine.
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PMID:In vitro homocysteine inhibits platelet Na+,K+-ATPase and serum butyrylcholinesterase activities of young rats. 1512 85

In the present study we investigate the effect of homocysteine (Hcy) administration, the main metabolite accumulating in homocystinuria, on butyrylcholinesterase (BuChE) activity in serum of rats. For the acute treatment, 29-day-old Wistar rats received one subcutaneous injection of Hcy (0.6 micromol/g) or saline (control) and were killed 1 h later. For the chronic treatment, Hcy was administered subcutaneously to rats from the 6th to the 28th day of life. Control rats received saline. The rats were killed 12 h after the last injection. In another set of experiments, rats were pretreated for one week with vitamins E and C or saline and 12 h after the last injection received one single injection of Hcy or saline, being killed 1 h later. Serum was used to determine BuChE activity. Our results showed that acute and chronic administration of Hcy significantly decreased BuChE activity. Furthermore, vitamins E and C per se did not alter BuChE activity, but prevented the reduction of this enzyme activity caused by acute administration of Hcy. The data suggest that the inhibitory effect of Hcy on BuChE activity is probably mediated by free radicals, since vitamins E and C administration prevented such effect.
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PMID:Reduction of butyrylcholinesterase activity in rat serum subjected to hyperhomocysteinemia. 1593 28

As the spectrum of therapeutic options broadens, the possibility of an early and accurate diagnosis of Alzheimer's disease (AD), or even isolation of a group at high risk of subsequent cognitive decline, is focusing widespread attention. Therefore, biological markers or risk factors of AD are highly desirable. In this work, we give an overview of the most extensively studied AD biomarkers, namely beta-amyloid, tau protein, and phosphorylated tau-protein, alone or in combination. Moreover, we describe the role of inflammatory markers (cytokines, acute phase proteins), oxidative stress markers (isoprostanes, 8-hydroxyguanine, 3-nitrotyrosine, plasma antioxidants, redox transition metals), homocysteine and related vitamins, cholesterol and 24S-hydroxycholesterol in the diagnostic process or prediction of AD. We briefly review less popular, though promising markers of AD - markers of apoptosis, neuronal thread protein, acetyl- and butyrylcholinesterase, sulfatide, kallikreins, matrix-degrading metalloproteinases, and novel isoforms of beta-amyloid and tau. Finally, we discuss the clinical applicability of AD-related biological markers.
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PMID:Biochemical markers and risk factors of Alzheimer's disease. 1597 89

The main objective of the present study was to evaluate the effect of folic acid pretreatment on parietal cortex Na(+),K(+)-ATPase and serum butyrylcholinesterase activities in rats subjected to acute hyperhomocysteinemia. Animals were pretreated daily with an intraperitoneal injection of folic acid (5 mg/kg) or saline from the 22th to the 28th day of age. Twelve hours after the last injection of folic acid or saline, the rats received a single subcutaneous injection of homocysteine (0.6 micromol/g of weight body) or saline and were killed 1h later. Serum was collected and the brain was quickly removed and parietal cortex dissected. Results showed that acute homocysteine administration significantly decreased the activities of Na(+),K(+)-ATPase and butyrylcholinesterase on parietal cortex and serum, respectively. Furthermore, folic acid pretreatment totally prevented these inhibitory effects. We also evaluated the effect of acute homocysteine administration on some parameters of oxidative stress, namely thiobarbituric acid-reactive substances and total thiol content in parietal cortex of rats. No alteration of these parameters were observed in parietal cortex of homocysteinemic animals, indicating that these oxidative stress parameters were probably not responsible for the reduction of Na(+),K(+)-ATPase and butyrylcholinesterase activities. The presented results confirm previous findings that acute hyperhomocysteinemia produces an inhibition of Na(+),K(+)-ATPase and butyrylcholinesterase activities and that pretreatment with folic acid prevents such effects. Assuming that homocysteine might also reduce the activities of these enzymes in human beings, our results support a new potential therapeutic strategy based on folic acid supplementation to prevent the neurological damage found in hyperhomocysteinemia.
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PMID:Folic acid pretreatment prevents the reduction of Na(+),K(+)-ATPase and butyrylcholinesterase activities in rats subjected to acute hyperhomocysteinemia. 1644 60

1. The cholinergic system is important in cognition and behavior as well as in the function of the cerebral vasculature. 2. Hyperhomocysteinemia is a risk factor for development of both dementia and cerebrovascular disease. 3. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) are serine hydrolase enzymes that catalyze the hydrolysis of the neurotransmitter acetylcholine, a key process in the regulation of the cholinergic system. 4. It has been hypothesized that the deleterious effects of elevated homocysteine may, in part, be due to its actions on cholinesterases. 5. To further test this hypothesis, homocysteine and a number of its metabolites and analogues were examined for effects on the activity of human cholinesterases. 6. Homocysteine itself did not have any measurable effect on the activity of these enzymes. 7. Homocysteine thiolactone, the cyclic metabolite of homocysteine, slowly and irreversibly inhibited the activity of human AChE. 8. Conversely, this metabolite and some of its analogues significantly enhanced the activity of human BuChE. 9. Structure-activity studies indicated that the unprotonated amino group of homocysteine thiolactone and related compounds represents the essential feature for activation of BuChE, whereas the thioester linkage appears to be responsible for the slow AChE inactivation. 10. It is concluded that hyperhomocysteinemia may exert its adverse effects, in part, through the metabolite of homocysteine, homocysteine thiolactone, which is capable of altering the activity of human cholinesterases, the most pronounced effect being BuChE activation.
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PMID:Homocysteine thiolactone and human cholinesterases. 1695 66

Current treatments for Alzheimer's disease involve inhibiting cholinesterases. Conversely, cholinesterase stimulation may be deleterious. Homocysteine is a known risk factor for Alzheimer's and vascular diseases and its active metabolite, homocysteine thiolactone, stimulates butyrylcholinesterase. Considering the opposing effects on butyrylcholinesterase of homocysteine thiolactone and cholinesterase inhibitors, understanding how these molecules alter this enzyme may provide new insights in the management of dementia. Butyrylcholinesterase does not strictly adhere to Michaelis-Menten parameters since, at higher substrate concentrations, enzyme activation occurs. The substrate activation equation for butyrylcholinesterase does not describe the effects of inhibitors or non-substrate activators. To address this, global data fitting was used to generate a flexible equation based on Michaelis-Menten principles. This methodology was first tested to model complexities encountered in inhibition by imidazole of beta-galactosidase, an enzyme that obeys Michaelis-Menten kinetics. The resulting equation was sufficiently flexible to permit expansion for modeling activation or inhibition of butyrylcholinesterase, while accounting for substrate activation of this enzyme. This versatile equation suggests that both the inhibitor and non-substrate activator examined here have little effect on the substrate-activated form of butyrylcholinesterase. Given that butyrylcholinesterase inhibition can antagonize stimulation of this enzyme by homocysteine thiolactone, cholinesterase inhibition may have a role in treating Alzheimer and vascular diseases related to hyperhomocysteinemia.
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PMID:A versatile equation to describe reversible enzyme inhibition and activation kinetics: modeling beta-galactosidase and butyrylcholinesterase. 1730 93

In the present study we investigated the effect of homocysteine administration, the main metabolite accumulating in homocystinuria, on cholinesterase activity in rat and human serum. For the in vivo study, 8-, 15- and 60-day-old rats received one subcutaneous injection of homocysteine (0.3, 0.4 or 0.6 micromol/g of body weight, respectively) or saline (control) and were sacrificed 1h later, when serum was collected in order to determine cholinesterase activity. For the in vitro studies, serum of 8-, 15- and 60-day-old untreated rats or 20-25- and 52-60-day-old human beings (healthy volunteers) were incubated with 10-500 microM homocysteine. Results showed that acute hyperhomocysteinemia (in vivo study) significantly reduced cholinesterase activity in the serum of rats of all ages tested. We also observed that 500 microM homocysteine added to the incubation medium (in vitro study) significantly inhibited cholinesterase activity both in serum of rats and humans. Our findings seem to reinforce the proposed associations of cholinesterase activity with hyperhomocysteinemia.
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PMID:Homocysteine reduces cholinesterase activity in rat and human serum. 1748 43

Mild cognitive impairment (MCI) and cognitive impairment, no dementia (CIND) might be the optimum stage at which to intervene with preventative therapies. This article reviews recent work on the possible treatment and presents evidence-based recommendations approved at the meeting of the Third Consensus Conference on the Diagnosis and Treatment of Dementia held in Montreal in March, 2006. A number of promising nonpharmacologic interventions have been examined. Associations exist with both cognitive and physical activity that suggest that both of these, together or separately, can delay progression to dementia. Similarly, case control studies as well as prospective long-term studies suggest a number of low toxicity interventions and supplements that might significantly impact on MCI progression; folate, B(6), and B(12) to lower homocysteine levels, omega-fatty acids, and anti-oxidants (fruit juices or red wine) are good examples. In selected genotypes such as individuals with APOE e4, therapy with donepezil might slow progression. The concern, however, is that none of these therapies (including cholinesterase inhibitors) have demonstrated a clinically meaningful effect with randomized, placebo-controlled studies. Just as randomized controlled studies have failed to support primary prevention of dementia by using estrogen or nonsteroidal anti-inflammatory drugs (NSAIDs), there exists the possibility that well-designed randomized controlled trials might fail to definitively demonstrate putative or promising mild cognitive impairment interventions. Pharmacologic interventions and nonpharmacologic therapies, while tantalizing, are currently for the most part insufficiently proven to allow serious consideration by physicians. Recommendation were supported for a general "healthy lifestyle" including physical exercise, healthy nutrition, smoking cessation, and mental stimulation. Close monitoring and treatment of vascular risk factors are justified and were also supported.
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PMID:Mild cognitive impairment and cognitive impairment, no dementia: Part B, therapy. 1959 49


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