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:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The enzymatic activity of acetylcholinesterase (AchE) in the cerebrospinal fluid (CSF) is considered to be a marker of central cholinergic neuron integrity. Then, we evaluated CSF AchE activity in 90 cases of neurological diseases involving cholinergic system and their related disease, and 28 control cases without central organic lesions or abnormal findings in routine CSF study. AchE activity was evaluated according to Ellman's method using acetylthiocholine iodide as a substrate and tetraisopropyl-pyrophosphoramide, a specific inhibitor of butyrylocholinesterase. CSF AchE of Alzheimer type dementia (AD/SDAT, N = 12: 21.9 +/- 4.7 nmol/ml/min) showed no significant change from those of both control group (22.1 +/- 3.9) and vascular dementia (9: 21.7 +/- 6.7). In extrapyramidal diseases, reduction of the activity was observed in Huntington's chorea (HC, 4: 16.3 +/- 1.4) and progressive supranuclear palsy (PSP, 4: 17.6 +/- 1.7), whereas normal activity was shown in Parkinson's disease (PD, 19: 22.5 +/- 4.6), dentatorubropallidoluysian atrophy (DRPLA, 4: 22.6 +/- 4.2) and striatonigral degeneration (SND, 4: 20.4 +/- 4.3). In olivopontocerebellar atrophy (OPCA, N = 16), we disclosed reduced CSF AchE activity (15.8 +/- 2.4) which had significant correlations with the atrophy of the pontine base (r = 0.6017, p less than 0.02) and cerebellar vermis (r = 0.5450, p less than 0.05) in MRI. AchE activity in cerebellar cortical atrophy (CCA, 5: 20.6 +/- 2.2) remained within the control values. Normal activity was demonstrated in both amyotrophic lateral sclerosis (6: 24.3 +/- 7.3) and spinal muscular atrophy (4: 22.9 +/- 3.9).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[CSF acetylcholinesterase activity in central neurological diseases involving cholinergic systems]. 162 49

The cholinergic innervation of the mediodorsal nucleus of the thalamus, which is thought to originate primarily in the laterodorsal tegmental nucleus and the substantia innominata, was studied by acetylcholinesterase histochemistry and immunohistochemistry with a polyclonal antiserum against human choline acetyltransferase on autopsy tissue from eight control subjects, five patients with progressive supranuclear palsy and four patients with senile dementia of Alzheimer type. In controls, cholinergic innervation of the mediodorsal nucleus of the thalamus was distributed heterogeneously in densely labelled patches surrounded by less heavily stained matrix. In patients with progressive supranuclear palsy, the density of choline acetyltransferase-positive varicosities decreased by 75% in the matrix and 60% in the patches. The number of choline acetyltransferase-positive cell bodies decreased by 84% in the laterodorsal tegmental nucleus, but more moderately (-33%) in the substantia innominata. In patients with senile dementia of Alzheimer type, choline acetyltransferase-positive varicosities decreased by 34% in the matrix, but 46% in the patches. Choline acetyltransferase-labelled cell bodies were spared in the laterodorsal tegmental nucleus, whereas severe loss (-80%) was observed in the substantia innominata. These results suggest that cholinergic innervation of mediodorsal nucleus matrix derives mainly from the laterodorsal tegmental nucleus and mediodorsal nucleus patches from the substantia innominata. Differential loss of innervation to the matrix and patches in progressive supranuclear palsy and senile dementia of Alzheimer type may in turn differentially affect mediodorsal nucleus innervation of the frontal cortex, resulting in dissimilar symptomatologies.
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PMID:Differential vulnerability of cholinergic projections to the mediodorsal nucleus of the thalamus in senile dementia of Alzheimer type and progressive supranuclear palsy. 205 62

The present study examined the effects of a glucocorticoid and a mineralocorticoid on organophosphorus-induced delayed neuropathy (OPIDN) as previous investigations have indicated that an endogenous steroid with both properties could alter this syndrome in chickens. The glucocorticoid triamcinolone and the mineralocorticoid deoxycorticosterone were provided in the diet beginning 1 day before and continuing 10 days after triortho-tolyl phosphate (TOTP, 360 mg/kg po), phenyl saligenin phosphate (PSP, 2.5 mg/kg im), and diisopropyl phosphorofluoridate (DFP, 1 mg/kg sc). In a manner similar to that seen with corticosterone, a low concentration (0.1 ppm) of triamcinolone reduced and a high concentration (10 ppm) exacerbated clinical signs. Concentrations of deoxycorticosterone under 80 ppm also partially delayed or ameliorated ataxia induced by TOTP, PSP, and DFP, but a combination of 0.1 ppm triamcinolone and 80 ppm deoxycorticosterone was not more effective than triamcinolone alone. Peripheral nerve damage was noted in all chickens given organophosphorus compounds, whether or not they had been given corticoids. Both steroids induced hydroxylase activity, but effects on most other enzyme systems examined were unremarkable. High concentrations of triamcinolone (10 ppm) could, however, also reduce liver cytochrome P450 levels and liver cholinesterase activity. Exacerbation of OPIDN was most notable in chickens under highest stress, as indicated by elevated heterophil-to-lymphocyte ratios. The clinical, pathological, biochemical, and hematological indices of exposure to adrenocorticoids and agents inducing OPIDN in chickens were, therefore, similar for both a synthetic glucocorticoid and the endogenous steroid corticosterone.
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PMID:Types of adrenocorticoids and their effect on organophosphorus-induced delayed neuropathy in chickens. 334 Oct 34

Inhibition of neuropathy target esterase (NTE, neurotoxic esterase) and acetylcholinesterase (AChE) activities was compared in brain and spinal cords of adult While Leghorn hens and adult male Long Evan rats 4-48 hr after administration of triortho-tolyl phosphate (TOTP po, 50-500 mg/kg to hens; 300-1000 mg/kg to rats), phenyl saligenin phosphate (PSP im 0.1-2.5 mg/kg to hens; 5-24 mg/kg to rats), mipafox (3-30 mg/kg ip to hens and rats), diisopropyl phosphorofluoridate (DFP sc, 0.25-1.0 mg/kg to hens; 1-3 mg/kg to rats), dichlorvos (5-60 mg/kg ip to hens; 600-2000 mg/kg to rats), and carbaryl (300-560 mg/kg ip to hens; 30-170 mg/kg to rats). Inhibitions of NTE and AChE were dose-related after administration of all compounds to both species. Hens and rats given TOTP, PSP, mipafox, and DFP demonstrated delayed neuropathy 3 weeks later, with spinal cord lesions and clinical signs more notable in hens. Ratios of NTE/AChE inhibition in hen spinal cord, averaged over the doses used, were 2.6 after TOTP, 5.2 after PSP, 1.3 after mipafox, and 0.9 after DFP, which contrast with 0.53 after dichlorvos, 1.0 after malathion, and 0.46 after carbaryl. Rat NTE/AChE inhibition ratios were 0.9 after TOTP, 2.6 after PSP, 1.0 after mipafox, 0.62 after DFP, 1.3 after dichlorvos, 2.2 after malathion, and 1.1 after carbaryl. The lower NTE/AChE ratios in rats given dosages of the four organophosphorus compounds that caused delayed neuropathy interferred with survival, an effect that was not a problem in hens.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of the relative inhibition of acetylcholinesterase and neuropathy target esterase in rats and hens given cholinesterase inhibitors. 771 47

125I-Nerve growth factor (NGF) binding sites were analyzed by autoradiography in the striatum of 3 control subjects, 3 patients with Parkinson's disease and 3 patients with progressive supranuclear palsy. A high level of 125I-NGF binding was observed (0.3-0.4 fmol/mg of tissue equivalent) in the striatum and the nucleus basalis of Meynert of control patients. Pockets of lower 125I-NGF binding corresponding to acetylcholinesterase-poor striosomes were detected in the striatum of control subjects and patients with Parkinson's disease or progressive supranuclear palsy. When compared to controls, the density of 125I-NGF binding sites was reduced by 30% in the striatum of patients with progressive supranuclear palsy but not reduced in that of patients with Parkinson's disease. 125I-NGF binding was not significantly decreased in the nucleus basalis of Meynert in either diseases. Since NGF receptors are thought to be localized on cholinergic neurons in the striatum, the decrease in NGF binding is compatible with the loss of cholinergic neurons reported in the striatum from PSP patients.
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PMID:Loss of striatal high affinity NGF binding sites in progressive supranuclear palsy but not in Parkinson's disease. 789 88

In spite of the severe loss of cholinergic neurons in the brains of patients with progressive supranuclear palsy (PSP), marginal or null benefits are seen in clinical trials after the administration of physostigmine, a cholinesterase inhibitor, or RS-86, a cholinergic agonist. The possible role of cholinergic therapy in PSP is reevaluated.
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PMID:Cholinergic approaches to the treatment of progressive supranuclear palsy. 796 92

The purpose of this pilot study was to investigate whether cholinergic stimulation reduces swallowing and oral motor disturbances in patients with progressive supranuclear palsy (PSP). A controlled, double-blind crossover trial of physostigmine, a centrally active cholinesterase inhibitor, and placebo was conducted. Patients were randomized to a 10-day crossover placebo-controlled double-blind trial of physostigmine at their previously determined best dose administered orally every 2 hr, six times per day. Patients were evaluated with ultrasound imaging of the oropharynx and an oral motor examination at baseline and during the third or fourth days of each study phase (placebo and drug). Under the double-blind placebo-controlled conditions, patients showed no statistically significant improvement in oral motor functions or swallow durations. Because patients with PSP have increased sensitivity to cholinergic blockade compared with control subjects, studies with newer, more potent cholinergic stimulating agents need further exploration. Suggestions for future research include the evaluation of newer direct cholinergic agonists in the treatment of the less-impaired PSP patients who may have a greater number of cholinergic neurons preserved and the evaluation of combined therapies.
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PMID:Effects of physostigmine on swallowing and oral motor functions in patients with progressive supranuclear palsy: A pilot study. 1034 Nov 15

Recently, we have developed a method to measure acetylcholinesterase (AChE) activity, a functional marker for cholinergic system, by positron emission tomography (PET) and carbon-11 labeled N-methyl-4-piperidyl acetate. Kinetic analysis of the radioactivity in the brain and the plasma yielded a rate constant "k 3" as an index of AChE activity. The ratios for the k 3 values for the cerebral cortex/thalamus/cerebellum/striatum found in healthy participants were 1/3/8/10, respectively, corresponding well with AChE activity ratios in the brain at necropsy (1/3/8/38), except for the striatum. In 23 healthy volunteers (age range: 24-89 years), there was no age-related decline of k 3 values in the cerebral cortex, suggesting AChE activity is preserved in aged cerebral cortex. In 11 patients with Alzheimer's disease, there was a significant reduction (-24%) of k 3 values in the cerebral cortex and hippocampus, suggesting a loss of ascending cholinergic system from the basal forebrain to the cerebral cortex and hippocampus. In 16 patients with Parkinson's disease, there was a significant reduction (-18%) of k 3 values in the cerebral cortex. In 10 patients with progressive supranuclear palsy, there was a significant reduction (-38%) of k 3 values in the thalamus. This technique is useful for investigating central cholinergic system in neurodegenerative disorders with dementia.
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PMID:[PET study of cholinergic system in the brain]. 1037 94

We measured brain acetylcholinesterase activity in 16 patients with Parkinson's disease (PD), 12 patients with progressive supranuclear palsy (PSP), and 13 age-matched controls, using N-methyl-4-[11C]piperidyl acetate and positron emission tomography. Kinetic analysis was performed to calculate k3, an index of acetylcholinesterase activity. In PD patients, there was a significant reduction (-17%) of cerebral cortical k3 compared with normal controls, whereas there was only a nonsignificant reduction (-10%) of cortical k3 in PSP patients. However, there was a prominent reduction (-38%) of thalamic k3 in PSP patients compared with normal controls, whereas there was only a nonsignificant reduction (-13%) of thalamic k3 in PD patients. The results suggest that there is a loss of cholinergic innervation to the cerebral cortex in association with cholinergic innervation to the thalamus in PD, whereas there is a preferential loss of cholinergic innervation to the thalamus in PSP. When the thalamic to cerebral cortical k3 ratio was taken for each subject, PD and PSP were separated, suggesting that positron emission tomography measurement of acetylcholinesterase activity may be useful for differentiating the two similar disorders.
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PMID:Positron emission tomographic measurement of acetylcholinesterase activity reveals differential loss of ascending cholinergic systems in Parkinson's disease and progressive supranuclear palsy. 1040 81

A new method for quantitative measurement of brain acetylcholinesterase (AChE) activity in living human brain using positron emission tomography (PET) is described. We tested several radiolabeled lipophilic acetylcholine analogs, e.g., N-methylpiperidyl esters, which readily entered the brain via the blood-brain barrier, were hydrolyzed selectively by AChE, and were then trapped in the brain. Among them, and tested and N-[11C]methylpiperidin-4-yl acetate ([11C]MP4A) was chosen as the tracer for PET. Quantitative measurement of cortical AChE was accomplished by fitting the time course of cerebral radioactivity concentration measured by PET and the metabolite-corrected arterial plasma input function using a nonlinear least-squares fitting method. Normal control studies of subjects with a wide range in age (24-89 years) showed no decrease in AChE activity in the cerebral cortex with age. Studies on patients with Alzheimer's disease demonstrated a widespread reduction of AChE activity in the cerebral cortex (more profound in early-onset than in late-onset Alzheimer's disease). Parkinson's disease and progressive supranuclear palsy, clinically similar disorders, could be differentiated with [11C]MP4A/PET studies. Simple methods without using an arterial input function are also proposed. The method provides a quantitative measure of the cholinergic aspect of brain function and proved to be useful in diagnosis of neurodegenerative disorders including Alzheimer's disease.
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PMID:Positron emission tomography: quantitative measurement of brain acetylcholinesterase activity using radiolabeled substrates. 1218 13


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