Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebral vascular tonus was measurably influenced by both alpha or beta adrenergic blockade and by inhibition of cerebrovascular acetylcholine or acetylcholinesterase. Cerebral autoregulatory response was significantly affected by intravenous injection of PBZ, intravertabral and intravenous injection of PPL and intravertebral and intracarotid injection of neostigmine. Cerebral vasomotor reactivity to changes in aPCO2 was altered significantly by intravertebral injection of PPL, atropine, and neostigmine. The doses of intravenous PBZ injections were large (1.5 mg/kg) so that PBZ not only blocked peripheral alpha adrenergic receptor sites in the cerebrovascular system but probably also those possibly located in the brain stem (vertebrobasilar territory). The functional significance of a double cholinergic and adrenergic neuronal system located in the brain stem influencing CBF appears to have been established.
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PMID:[Double cholinergic and adrenergic regulation of cerebral blood flow]. 81 35

Alzheimer's disease is the most common cause of dementia, but Parkinson's disease also shows dementia in the later stages. Donepezil is a cholinesterase inhibitor used for the treatment of Alzheimer's disease. Variable responses to this drug suggest that Alzheimer's disease is clinically heterogeneous. In the clinical trial of tacrine, a first developed cholinesterase inhibitor, three cases markedly improved and, several years later, they were pathologically confirmed as dementia with Lewy bodies (DLB). In recent years, another cholinesterase inhibitor, rivastigmine, has also been reported to be effective for patients with DLB by a placebo-controlled, double-blind, multicenter study. Parkinson's disease with dementia, which is known to fulfill the pathological criteria of DLB, also shows a favorable response to donepezil. In some cases, not only does cognitive function improve, but also parkinsonism. Both DLB and Parkinson's disease with dementia show characteristic CBF patterns: While the parietal and temporal lobes are involved in Alzheimer's disease, the occipital lobe is additionally affected in these diseases. Alzheimer's disease and Parkinson's disease have been considered discrete disease entities. However, viewed from the aspects of response to donepezil treatment and CBF patterns, both diseases overlapped. A brain SPECT may be a useful tool to detect such treatable conditions.
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PMID:Responses to donepezil in Alzheimer's disease and Parkinson's disease. 1248 Jul 91

We have recently reported that acetylcholinesterase expression was induced during apoptosis in various cell types. In the current study we provide evidence to suggest that the induction of acetylcholinesterase expression during apoptosis is regulated by the mobilization of intracellular Ca(2+). During apoptosis, treatment of HeLa and MDA-MB-435s cells with the calcium ionophore A23187 resulted in a significant increase in acetylcholinesterase mRNA and protein levels. Chelation of intracellular Ca(2+) by BAPTA-AM (1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester), an intracellular Ca(2+) chelator, inhibited acetylcholinesterase expression. A23187 also enhanced the stability of acetylcholinesterase mRNA and increased the activity of acetylcholinesterase promoter, effects that were blocked by BAPTA-AM. Perturbations of cellular Ca(2+) homeostasis by thapsigargin resulted in the increase of acetylcholinesterase expression as well as acetylcholinesterase promoter activity during thapsigargin induced apoptosis in HeLa and MDA-MB-435s cells, effects that were also inhibited by BAPTA-AM. We further demonstrated that the transactivation of the human acetylcholinesterase promoter by A23187 and thapsigargin was partially mediated by a CCAAT motif within the -1270 to -1248 fragment of the human acetylcholinesterase promoter. This motif was able to bind to CCAAT binding factor (CBF/NF-Y). These results strongly suggest that cytosolic Ca(2+) plays a key role in acetylcholinesterase regulation during apoptosis induced by A23187 and thapsigargin.
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PMID:Regulation of acetylcholinesterase expression by calcium signaling during calcium ionophore A23187- and thapsigargin-induced apoptosis. 1700 Jan 30

We previously reported that the expression of acetylcholinesterase during A23187-induced apoptosis of HeLa cells is regulated by Ca(2+) mobilization through the modulation of mRNA stability and acetylcholinesterase promoter activity. Transactivation of the human acetylcholinesterase promoter by A23187 was partially mediated by the distal CCAAT motif within the -1270 to -1248 fragment of the human acetylcholinesterase promoter, which was bound by the CCAAT binding factor (CBF/NF-Y). In the present study, we investigated the molecular mechanisms by which CBF/NF-Y regulates A23187-induced activation of the human acetylcholinesterase promoter. The results indicate that CBF/NF-Y binding to the distal CCAAT motif suppresses the promoter activity. Electrophoretic mobility shift assays (EMSAs) demonstrated that binding of CBF/NF-Y to the distal CCAAT motif decreased after A23187 treatment. Our results suggest that acetylcholinesterase promoter activation during A23187-induced HeLa cell apoptosis may result partly from the dissociation of CBF/NF-Y from the distal CCAAT motif in the acetylcholinesterase promoter, reversing this suppression.
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PMID:The CCAAT-binding factor CBF/NF-Y regulates the human acetylcholinesterase promoter activity during calcium ionophore A23187-induced cell apoptosis. 1772 68

This study is to investigate changes in regional cerebral blood flow (rCBF) of Alzheimer's disease (AD) in short-term treatment with acetylcholinesterase inhibitor (ChEI). rCBF was measured by single photon emission computed tomography (SPECT). CBF measurements were performed in 13 AD patients before treatment and 4 months later, while the control group with syncope or headache consisted of 17 patients. The clinical diagnosis of AD was based on the NINCDS-ADRDA criteria. Significant increases in rCBF were noted in the left angular, the right superior frontal gyrus, the right occipital, the left temporal lobe and the left orbital gyrus at the end of short-term therapy. Reduction in the rCBF before treatment is more profound in the left superior temporal, the right precentral and the both inferior frontal gyri compared with the control group. It achieved increase of rCBF after ChEI treatment. Also it overall increased in global cognitive functions including Korean Version Mini Mental State Examination (K-MMSE) and Clinical Dementia Rating (CDR). Treatment with ChEI for 4 months could increase rCBF and improve cognitive function of patients with AD.
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PMID:The short-term effect of acetylcholinesterase inhibitor on the regional cerebral blood flow of Alzheimer's disease. 1939 34