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)

A 42-year-old housewife with myasthenia gravis (MG) for 22 years, who was initially treated by radiation to the hyperplastic thymus and anti-cholinesterase therapy, developed bilateral ptosis, paresthesia of her right face and decreased taste sensation after house work at the age of 42 years. Neurological examinations revealed lateral and vertical gaze palsy, upward nystagmus, decreased taste sensation, peripheral facial palsy on the left side. She also had hypalgesia on the right face, arm and chest up to Th7 level, and urinary retention. She had hyperreflexia on the right side but no extensor toe signs. CSF study revealed 5 cells/microliters and protein of 23 mg/dl. Serum IgG anticardiolipin antibody was positive. Magnetic resonance imaging studies revealed high intensity areas in the brainstem tegmentum and periventricular white matter. Diagnosis of multiple sclerosis (MS) was made. This is the first case in which MG, MS and serum anticardiolipin antibody were present simultaneously, which may be all due to some immunological abnormality. Steroid therapy made anti-cardiolipin antibody negative, but new MS plaque developed in 7 months, which favors diagnosis of MS rather than infarction, since the activities of ACLA were not correlating to clinical symptoms. MRI was helpful in detecting MS plaques in MG patients.
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PMID:[A case of myasthenia gravis associated with multiple sclerosis and positive anticardiolipin antibodies]. 836 70

Neurofibrillary tangles and amyloid plaques express acetylcholinesterase and butyrylcholinesterase activity in Alzheimer disease. We previously reported that traditional acetylcholinesterase inhibitors such as BW284C51, tacrine, and physostigmine were more potent inhibitors of the acetylcholinesterase in normal axons and cell bodies than of the acetylcholinesterase in plaques and tangles. We now report that the reverse pattern is seen with indoleamines (such as serotonin and its precursor 5-hydroxytryptophan), carboxypeptidase inhibitor, and the nonspecific protease inhibitor bacitracin. These substances are more potent inhibitors of the cholinesterases in plaques and tangles than of those in normal axons and cell bodies. These results show that the enzymatic properties of plaque and tangle-associated cholinesterases diverge from those of normal axons and cell bodies. The selective susceptibility to bacitracin and carboxypeptidase inhibitor indicates that the catalytic sites of plaque and tangle-bound cholinesterases are more closely associated with peptidase or protease-like properties than the catalytic sites of cholinesterases in normal axons and cell bodies. This shift in enzymatic affinity may lead to the abnormal protein processing that is thought to play a major role in the pathogenesis of Alzheimer disease. The availability of pharmacological and dietary means for altering brain indoleamines raises therapeutic possibilities for inhibiting the abnormal cholinesterase activity associated with Alzheimer disease.
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PMID:Protease inhibitors and indoleamines selectively inhibit cholinesterases in the histopathologic structures of Alzheimer disease. 842 6

The colocalization of beta amyloid protein with the enzymes acetyl- and butyrylcholinesterase was assessed using immunocytochemistry for beta amyloid protein and a sensitive histochemical technique for cholinesterases. In non-demented aged and Alzheimer's disease brains, double-stained sections for cholinesterases and thioflavin-S showed that all thioflavin-S-positive plaques were also positive for cholinesterases, indicating the presence of these enzymes in all plaques with beta-pleated amyloid protein. When amyloid angiopathy was present, cholinesterases were also observed in amyloid-laden vessels walls. Comparison of series of adjacent sections alternatively stained for acetylcholinesterase, beta amyloid protein and butyrylcholinesterase, as well as by double histo-immunocytochemical staining, showed either cholinesterase in a proportion of the preamyloid diffuse plaques. These data indicate that cholinesterases are associated with the amyloid protein from very early stages, when the beta-pleated structure is being formed. Novel functions attributed to acetyl- and butyrylcholinesterase, such us their proteolytic activity either by themselves or in association with heparan sulfate proteoglycans, may play a role in the aggregation or the consolidation processes taking place at the early stages of diffuse plaque formation.
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PMID:Colocalization of cholinesterases with beta amyloid protein in aged and Alzheimer's brains. 848 May 10

The senile plaque in Alzheimer's disease (AD) consists mainly of the amyloid beta-peptide (A beta) derived from a family of large integral membrane glycoproteins, beta-amyloid precursor proteins (beta APP). Soluble derivatives of beta APP generated by the proteolytic processing of full-length beta APP are normally secreted into the conditioned medium of cultured cells. Here we have investigated the possibility that the processing of beta APP can be regulated by the cholinesterase inhibitors physostigmine and tacrine. Both drugs mildly improve cognitive functions in some patients with AD. We analyzed the level of beta APP in glial, neuroblastoma, and pheochromocytoma cells by immunoblotting cell lysates and conditioned media using a monoclonal antibody, MAb22C11. The levels of soluble beta APP derivatives normally present in conditioned media were severely inhibited by treating cells with tacrine but not with physostigmine. Whereas the treatment of cells with tacrine resulted in a small decrease in the intracellular levels of beta APP, treating cells with physostigmine resulted in a slight increase in the intracellular levels of beta APP compared to untreated cells. The effect of tacrine on the secretion of beta APP was not affected by cotreating cells with muscarinic agents, staurosporine, or the calcium ionophore. Our results suggest that a decrease in the secretion of beta APP by tacrine did not depend on its anticholinesterase activity and that tacrine operates via a noncholinergic mechanism.
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PMID:Differential effect of tacrine and physostigmine on the secretion of the beta-amyloid precursor protein in cell lines. 883 81

Fenitrothion was administered orally to mice or rats in daily doses of up to 1/25 of the LD50 for 14 days, and numbers of splenic plaque-forming cells against sheep red blood cells (SRBC-PFC), one of the most common immune parameters, were measured. Splenic SRBC-PFC number was suppressed by fenitrothion only in rats which received 30 mg/kg body weight (bw) of the compound. Other immune parameters, including the arthus reaction, delayed-type hypersensitivity, and activities of macrophages and natural killer cells in rats, were not influenced by fenitrothion. Adrenal hyperfunction manifesting as increased organ weight and elevated plasma corticosterone level was noted along with strong cholinergic signs in rats which received 30 mg/kg bw of fenitrothion. At lower doses such as 3 or 0.3 mg/kg bw of fenitrothion, rats had no strong cholinergic signs, adrenal hyperfunction, or evidence of immunosuppression despite significant suppression of systemic cholinesterase (ChE) activities. In mice, no suppression of SRBC-PFC number or mixed lymphocyte reaction was noted even at the highest dose (40 mg/kg bw) of fenitrothion, at which significant suppression of systemic ChE activities but no cholinergic signs were noted. These findings strongly suggest that the immunosuppressive effect of fenitrothion noted in rats was due to systemic, potent cholinergic stress and that fenitrothion has no immunotoxicity in mice and rats.
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PMID:Immunotoxicological insignificance of fenitrothion in mice and rats. 892 43

The senile plaque in Alzheimer's disease (AD) consists mainly of the amyloid beta-peptide (A beta) derived from a larger beta-amyloid precursor protein (betaAPP). The majority of betaAPP is processed by either a secretory or lysosomal/endosomal pathway. Soluble derivatives of betaAPP (sAPP) and A beta generated by the proteolytic processing of full-length betaAPP are normally secreted into the conditioned medium of cultured cells. Tacrine, a centrally active potent cholinesterase inhibitor that has been shown to improve cognitive functions in some patients with AD, inhibits the secretion of sAPP. Here we have investigated whether leupeptin, a lysosomal protease inhibitor, could influence this effect of tacrine. We analyzed levels of betaAPP derivatives in cultured HeLa cells by immunoblotting cell lysates and conditioned media using the monoclonal antibody 22C11. Levels of sAPP normally present in conditioned media were severely reduced by treating cells with tacrine. The treatment of cells with tacrine resulted in a small decrease in the intracellular levels of betaAPP. The effect of treating the cells with tacrine did not depend upon the growing state of the cells as a similar effect was observed when the drug was added either during initial plating of the cells or after the attachment of the cells. The effect of tacrine was not affected by preincubating the cells with low serum in the culture medium. The treatment of cells with tacrine plus leupeptin reduced the secretion of sAPP in the medium to the same degree as did the treatment with tacrine alone, suggesting that the tacrine-mediated inhibition of sAPP release may not involve leupeptin-sensitive proteolytic pathways. The results suggest that the inhibitory effect of tacrine on sAPP secretion is not due to the proteolytic cleavage of the holoprotein in the medium.
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PMID:The effect of tacrine and leupeptin on the secretion of the beta-amyloid precursor protein in HeLa cells. 936 5

Deposits of diffuse beta-amyloid (Abeta) may exist in the brain for many years before leading to neuritic degeneration and dementia. The factors that contribute to the putative transformation of the Abeta amyloid from a relatively inert to a pathogenic state remain unknown and may involve interactions with additional plaque constituents. Matching brain sections from 2 demented and 4 nondemented subjects were processed for the demonstration of Abeta immunoreactivity, butyrylcholinesterase (BChE) enzyme activity, and thioflavine S binding. Additional sections were processed for the concurrent demonstration of two or three of these markers. A comparative analysis of multiple cytoarchitectonic areas processed with each of these markers indicated that Abeta plaque deposits are likely to undergo three stages of maturation, ie, a "diffuse" thioflavine S-negative stage, a thioflavine S-positive (ie, compact) but nonneuritic stage, and a compact neuritic stage. A multiregional analysis showed that BChE-positive plaques were not found in cytoarchitectonic areas or cortical layers that contained only the thioflavine S-negative, diffuse type of Abeta plaques. The BChE-positive plaques were found only in areas containing thioflavine S-positive compact plaques, both neuritic and nonneuritic. Within such areas, almost all (>98%) BChE-containing plaques bound thioflavine S, and almost all (93%) thioflavine S plaques contained BChE. These results suggest that BChE becomes associated with amyloid plaques at approximately the same time that the Abeta deposit assumes a compact beta-pleated conformation. BChE may therefore participate in the transformation of Abeta from an initially benign form to an eventually malignant form associated with neuritic tissue degeneration and clinical dementia.
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PMID:Butyrylcholinesterase in the life cycle of amyloid plaques. 940 84

The polymorphic K variant of the butyrylcholinesterase ( BCHE-K ) gene recently has been demonstrated to have an elevated frequency in Alzheimer's disease (AD) patients carrying the epsilon4 allele of the apolipoprotein (APO E) gene when compared with a control population. We therefore genotyped a large series of pathologically confirmed AD patients and controls to confirm this association. We found no change in the frequency of this genetic variant, either in the AD group as a whole or in early- or late-onset patients when compared with age-matched controls. Stratification of these groups with reference to the APO E epsilon4 allele also showed no difference between AD and control groups. To determine if a biological effect were present, we also looked at senile plaque and neurofibrillary tangle densities in the frontal, temporal, parietal and occipital cortices in AD patients either carrying or not carrying a copy of the K variant. We found no difference in plaque or tangle load between these two groups in either the total, late-onset or early-onset AD subjects. Stratification of the total AD group in terms of APO E epsilon4 allele possession, and further comparison of plaque and tangle load between carriers and non-carriers of BCHE-K still failed to disclose a relationship between BCHE-K and AD. We conclude that in the population studied here there is no association between BCHE-K and AD, or that if such a relationship exists it is precluded by another, as yet unknown factor.
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PMID:No association between the K variant of the butyrylcholinesterase gene and pathologically confirmed Alzheimer's disease. 953

A prominent feature of Alzheimer's disease (AD) pathology is an abundance of activated glia (astrocytes and microglia) in close proximity to the amyloid plaques. These activated glia overexpress a number of proteins that may participate in the progression of the disease, possibly by propagation of inflammatory and oxidative stress responses. The beta-amyloid peptide 1-42 (Abeta), a major constituent of neuritic plaques, can itself induce glial activation. However, little is known about whether other plaque components, especially the upregulated glial proteins, can induce glial activation or modulate the effects of Abeta on glia. In this study, we focused on four glial proteins that are abundant in amyloid plaques and/or that are known to interact with Abeta: alpha1-antichymotrypsin (ACT), interleukin-1beta (IL-1beta), S100beta, and butyrylcholinesterase (BChE). We examined the ability of these proteins to activate rat cortical astrocyte cultures and to influence the ability of Abeta to activate astrocytes. Treatment of astrocytes with ACT, IL-1beta, or S100beta resulted in glial activation, as assessed by reactive morphology, upregulation of IL-1beta, and production of inducible nitric oxide synthase and nitric oxide. The ability of Abeta to induce astrocyte activation was also enhanced in the presence of each of these three proteins. In contrast, BChE alone did not activate astrocytes and had no effect on Abeta-induced activation. These results suggest that certain proteins produced by activated glia may contribute to the chronic glial activation seen in AD through their ability to stimulate astrocytes directly or through their ability to modulate Abeta-induced activation.
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PMID:Glial-derived proteins activate cultured astrocytes and enhance beta amyloid-induced glial activation. 1052 94

In confirmed late-onset (>65 years) Alzheimer's disease, we found a greater load, both of overall neuritic plaques and of cholinesterase-positive neuritic plaques, in the temporal cortex of carriers of the butyrylcholinesterase K variant (BCHE-K) aged <80 years than of all other patients. The differences were most striking in the case of cholinesterase-positive neuritic plaques. Among BCHE-K carriers, densities of such plaques were over six times higher in patients <80 years at death than in those >80 years (P=0.01). Furthermore, in subjects <80 years, BCHE-K carriers had nearly six-fold greater densities of these plaques than non-carriers (P=0.009). We consider three potential explanations for these findings: that the K variant binds more readily to plaque constituents, that it promotes fibril formation or that it induces aberrant neurite growth.
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PMID:Association of butyrylcholinesterase K variant with cholinesterase-positive neuritic plaques in the temporal cortex in late-onset Alzheimer's disease. 1083 Sep 13


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