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)

Several neurotransmitter markers were investigated in the cerebrospinal fluid (CSF) from patients with Alzheimer's disease (AD) (n = 27), Parkinson's disease (PD) (n = 35) and ALS (n = 26) and from control subjects (n = 34) to compare the possible alterations in the biochemical profiles of these different neurodegenerative diseases. The main proportion of the patients represented an early phase of the illness at the time of the diagnosis. Correlations of the degree of dementia and the stage of the disease with CSF measures were evaluated. The CSF levels of somatostatin like-immunoreactivity (SLI) were significantly reduced in AD patients when compared with those of normals and ALS patients. The CSF concentrations of homovanillic acid (HVA) were significantly decreased for PD patients and the decrease focused on the non-demented patients. A trend of decreasing HVA values towards the most advanced stage of Parkinson's disease assessed by Webster's scale was also displayed. The content of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the CSF was higher for ALS patients than for other groups. The lowest 5-hydroxy-indoleacetic acid (5HIAA) levels were observed in the PD group and the lowest acetylcholinesterase (AChE) activities were found in the PD patients with the most severe disease. Changes in CSF measures were too subtle to be beneficial for diagnostic purposes, but adequate for reflecting the different neurochemical profiles of these three degenerative neurological disorders.
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PMID:Neurochemical markers in the cerebrospinal fluid of patients with Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis and normal controls. 134 20

Serum acetylcholinesterase (AChE) and pseudocholinesterase (ChE) activity in infantile and juvenile spinal muscular atrophy (SMA) was determined. The total AChE activity was either normal or decreased in the childhood SMA (Type 1), the other SMA groups and disease controls (ALS, X-linked SMA). In the majority of SMA Type 1 cases (6/7 tested) an absence of the asymmetric A12 form was found. This was accompanied by changes in the other asymmetric and globular forms. The latter was, however, not specific for SMA Type 1 cases. The ChE activity was increased in the majority of SMA cases as well as disease controls. The asymmetric A12 ChE form was increased in all SMA Type 3 cases, the values of this form in SMA Type 1 was variable. A change in the ChE globular forms in SMA Type 1 and SMA Type 2 was a frequent finding. It is suggested that the absence of the asymmetric A12 AChE form in SMA Type 1 arises because of muscle cell immaturity and undeveloped muscle-nerve interactions. The reason of ChE changes is obscure.
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PMID:Serum cholinesterase activity in infantile and juvenile spinal muscular atrophy. 280 Oct 18

To study the mechanisms by which glutamate-elicited acetylcholinesterase release (GEAR) might play a part in the pathogenesis of excitotoxically triggered motor neurone disease, and to investigate the interaction of GEAR with spinal glycinergic mechanisms, we measured acetylcholinesterase (AChE) and cholinergic markers, after stimulating ventral horn slices and synaptosomes from the mouse spinal cord, with both glutamate- and glycine-receptor agonists. Glutamate (GLU), kainate and AMPA, as well as glycine (GLY) evoked dose-related, calcium-dependent liberation of soluble forms of AChE from both slices and synaptosomes. GLY-evoked AChE release showed remarkable age-related postnatal changes. In the immature slice of the ventral horn. GLY potentiated the GEAR response in the presence of strychnine, suggesting N-methyl-D-aspartate (NMDA) receptor involvement, and was also able to evoke a strychnine-sensitive AChE release in the absence of exogenous GLU. After the 28th postnatal day, nearly all the AChE secreted was released either after the activation of non-NMDA glutamate receptors or by strychnine-sensitive GLY-evoked AChE release mechanisms. Both GEAR and GLY-evoked AChE release might impair the negative feedback loop which modulates the overactivation of motor neurones, and cause prolonged extracellular rises of soluble AChE. These effects might augment the vulnerability of motor neurones to excitotoxic stress, promote fiber outgrowth, and eventually accelerate the metabolic exhaustion of lower motor neurones. It is possible that the mechanisms described are operative at the spinal cord of ALS/MND patients.
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PMID:Glycine effects on glutamate-receptor elicited acetylcholinesterase release from slices and synaptosomes of the spinal ventral horn. 889 63

The involvement of the immune system in the pathogenesis of amyotrophic lateral sclerosis is controversial. It has been suggested that ALS patients develop specific antibodies against acetylcholinesterase (AChE) and that these antibodies by retrograde axonal transport may be the cause of death of the spinal motor neurons. It has also been argued that these antibodies elicit hemolysis of erythrocytes. However, using recombinant human AChE as antigen in ELISA and Western blot analysis, we have been unable to find any evidence for the existence of specific AChE antibodies in ALS patients.
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PMID:Autoimmunity and ALS: studies on antibodies to acetylcholinesterase in sera. 905 31

We have proposed that neuronal overactivation by either stimulation of excitatory receptors or hypofunction of inhibitory circuits is a cause of excessive acetylcholinesterase (AChE) release, which, in turn, can contribute to ALS/MND pathogenesis. We investigated histochemical and histopathological changes in cell populations of the mouse spinal ventral horn upon in vivo stimulation of glutamate receptors with L-aspartate (ASP, 10-50 mg/kg, intraperitoneal: i.p.), or blockade of glycine receptors with strychnine (STRY, 2 mg/kg, i.p.). ASP in P4-P13 (postnatal age in days) but not in older mice, and STRY irrespective of age, provoked rapid, striking depletions of motor neurone AChE, and appearance of AChE activity in astrocytes. This was followed by recovery of the enzyme in most motor neurones, astrocyte activation and statistically significant changes in: brain macrophage infiltration, loss of interneurones and motor neurones and neuronophagic images including rosettes of glial cells surrounding a central 'ghost-like' motor neurone. Although AChE release preceded the neuropathology found, it is not known if its uptake is a cause of glial activation. However, it has been shown that the enzyme potentiates non-N-metyl-D-aspartate receptors identical to those that mediate astrocyte activation. AChE activity produces protons and choline, possible microglial activators. These are putative routes towards long-lasting neuropathology.
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PMID:Motor neurone acetylcholinesterase release precedes neurotoxicity caused by systemic administration of excitatory amino acids and strychnine. 985 55

We previously reported that alpha-motor neurons in organotypic cultures of rat spinal cord (OTC-SC) are resistant to excitotoxicity induced through NMDA receptors. Here we describe the effects of non-NMDA glutamate receptor agonists kainic acid (KA) and quisqualic acid (QUIS) on motor neurons in OTC-SC. Large ventral horn acetylcholinesterase-positive neurons (VHANs), most of which are motor neurons, were quite sensitive to QUIS and KA toxicity and displayed losses of 95% and 94%, respectively. Small VHANs were reduced by 41% and 61% only. Identical results were obtained in cultures stained for non-phosphorylated neurofilaments. These observations demonstrate that alpha-motor neurons are considerably more sensitive to KA and QUIS than to NMDA toxicity. The proposed excitotoxic mechanism of ALS, therefore, is most likely mediated through non-NMDA glutamate receptors.
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PMID:Selective vulnerability of spinal cord motor neurons to non-NMDA toxicity. 1079 Aug 92

The present study demonstrated that administration of nicotine prevented glutamate-induced motor neuronal death in primary cultures of the rat spinal cord. The nicotine-induced neuroprotection was inhibited by either dihydro-beta-erythroidin (DHbetaE) or alpha-bungarotoxin (alphaBT), suggesting that it is mediated through both alpha4beta2 and alpha7 nicotinic acetylcholine receptors (nAChRs). Both alpha4beta2 and alpha7 nAChRs were identified on rat spinal motor neurons by immunohistochemical methods. We also demonstrated that galantamine, an acetylcholinesterase inhibitor with allosteric nAChR-potentiating ligand properties, prevented glutamate-induced motor neuronal death. These results suggest that stimulation of nAChR may be used as a treatment for ALS.
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PMID:Stimulation of nicotinic acetylcholine receptors protects motor neurons. 1582 82

The nature of toxic effects exerted on neurons by misfolded proteins, occurring in a number of neurodegenerative diseases, is poorly understood. One approach to this problem is to measure effects when such proteins are expressed in heterologous neurons. We report on effects of an ALS-associated, misfolding-prone mutant human SOD1, G85R, when expressed in the neurons of Caenorhabditis elegans. Stable mutant transgenic animals, but not wild-type human SOD1 transgenics, exhibited a strong locomotor defect associated with the presence, specifically in mutant animals, of both soluble oligomers and insoluble aggregates of G85R protein. A whole-genome RNAi screen identified chaperones and other components whose deficiency increased aggregation and further diminished locomotion. The nature of the locomotor defect was investigated. Mutant animals were resistant to paralysis by the cholinesterase inhibitor aldicarb, while exhibiting normal sensitivity to the cholinergic agonist levamisole and normal muscle morphology. When fluorescently labeled presynaptic components were examined in the dorsal nerve cord, decreased numbers of puncta corresponding to neuromuscular junctions were observed in mutant animals and brightness was also diminished. At the EM level, mutant animals exhibited a reduced number of synaptic vesicles. Neurotoxicity in this system thus appears to be mediated by misfolded SOD1 and is exerted on synaptic vesicle biogenesis and/or trafficking.
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PMID:An ALS-linked mutant SOD1 produces a locomotor defect associated with aggregation and synaptic dysfunction when expressed in neurons of Caenorhabditis elegans. 1916 29

We undertook a longitudinal study of the histological and biochemical changes at the neuromuscular junction (NMJ) in muscles of SOD1-G93A mice. We also assessed these functions in mice treated with a known heat shock protein inducer, arimoclomol. Tissue samples of treated and untreated mSOD mice were analysed for AChE and ChAT enzyme activities as markers of neuromuscular function. Sections of hindlimb muscles (TA, EDL and soleus) were also stained for succinate dehydrogenase and silver cholinesterase activities as well as for immunohistochemistry. Hsp70 levels were also measured from muscle samples using ELISA. Results showed that denervation and nerve sprouting were present at symptom onset in fast muscles, although slow muscles remained fully innervated. Cholinergic enzyme activities were reduced prior to denervation and declined further with disease progression. Reduction of endplate size, a slow to fast shift in muscle phenotype was also observed. Treatment with arimoclomol delayed the appearance of these changes, increased innervation, cholinergic enzyme activities and endplate size and reversed muscle fibre transformation. These beneficial effects of arimoclomol in muscles were accompanied by an increase in Hsp70 expression. In conclusion, our results indicate that pharmacological targeting of muscles at early stages of disease may be a successful strategy to ameliorate disease progression in ALS.
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PMID:Treatment with a coinducer of the heat shock response delays muscle denervation in the SOD1-G93A mouse model of amyotrophic lateral sclerosis. 2259 Nov 94

Variations in the enzyme activity of acetylcholinesterase (AChE) in the presence of the nano-material, graphene oxide (GO), were investigated with the use of molecular spectroscopy UV-visible and fluorescence methods. From these studies, important kinetic parameters of the enzyme were extracted; these were the maximum reaction rate, Vm , and the Michaelis constant, Km . A comparison of these parameters indicated that GO inhibited the catalytic activity of the AChE because of the presence of the AChE-GO complex. The formation of this complex was confirmed with the use of fluorescence data, which was resolved with the use of the MCR-ALS chemometrics method. Furthermore, it was found that the resonance light-scattering (RLS) intensity of AChE changed in the presence of GO. On this basis, it was demonstrated that the relationship between AChE and GO was linear and such models were used for quantitative analyses of GO.
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PMID:Inhibition effect of graphene oxide on the catalytic activity of acetylcholinesterase enzyme. 2562 Jul 14


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