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)

Alzheimer's disease (AD) is the most common type of dementia disorder of elderly affecting millions of people. The pathophysiology of the disease is complex and involves multiple pathways of neuronal damage. Sporadic dementia of Alzheimer's type (SDAT) has been shown to be associated with microtubular dysfunction and is characterized by the appearance of specific cytoskeletal cellular abnormalities, including neurofibrillary tangles and senile plaques. Intracerebroventricular (i.c.v) administration of colchicine, a microtubule-disrupting agent, causes cognitive dysfunction as evidenced by poor retention of memory in both Morris water maze and elevated plus-maze task paradigms that is associated with excessive free radical generation. Biochemical analysis revealed that icv colchicine injection significantly induced lipid peroxidation, increased nitrite and depleted reduced glutathione (GSH) and acetylcholinesterase (AChE) level in rat brains. Chronic treatment with rivastigmine (0.625 and 2.5 mg/kg, po) twice daily for a period of 25 days beginning 4 days prior to colchicine injection significantly improved the colchicine-induced cognitive impairment and reduced AChE level. The results of the present study clearly indicated that colchicines-induced cognitive impairment and oxidative stress in animals and can be used as an animal model for drug screening for Alzheimer's disease.
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PMID:Colchicines-induced neurotoxicity as an animal model of sporadic dementia of Alzheimer's type. 1765 27

Inflammatory injury and induction of oxidative stress have been implicated as causative factors in neurodegenerative diseases such as Alzheimer's disease (AD). Using LPS-stimulated RAW 264.7 macrophages as a model of inflammatory injury, LPS was found to stimulate ROS production (159%), GSH depletion (15%) and loss of mitochondrial activity (32%) as well as TNFalpha release (40%), and NO production (13.7 times), all parameters involved in AD. PMS777, a tetrahydrofuran derivative, designed as a dual PAF and acetylcholinesterase inhibitor, was found to decrease ROS (up to 32%) and NO production (up to 5 times), TNFalpha release (33%). PMS777 also prevents loss of mitochondrial activity, and GSH depletion. In contrast, tacrine was found to decrease ROS production (57% up to 102%) and TNFalpha level (up to 30%). It decreases NO release only at the highest concentrations without preventing loss of mitochondrial activity and GSH depletion. In this study, we show that PMS777 is strongly anti-inflammatory against LPS-induced responses in RAW 264.7. Differential effects between PMS777 and tacrine could be attributed to the anti-PAF activity of PMS777 which was able to fight inflammatory events and oxidative injury whereas tacrine only minimizes them. PMS777 could open a new approach in the treatment of AD.
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PMID:A new acetylcholinesterase inhibitor with anti-PAF activity modulates oxidative stress and pro-inflammatory mediators release in stimulated RAW 264.7 macrophage cells. Comparison with tacrine. 1799 78

Ischemic stroke is a leading cause of mortality and disability particularly in the elderly. Hypertension is the most important risk factor in strokes, representing roughly 70% of all cases. Oxidative stress is believed to be one of the mechanisms taking part in neuronal damage in stroke. It is well documented that cholinergic system plays a key role in normal brain functions and in memory disturbances of several pathological processes, such as in cerebral blood flow regulation. This study investigated the oxidative status and acetylcholinesterase (AChE) activity in whole blood in patients diagnosed with acute and chronic stages of ischemia, as well as with hypertension. Malondialdehyde (MDA) levels and protein carbonylation content showed increased levels both in the acute ischemic groups and in the hypertensive group, when compared to the control. Catalase activity and reduced glutathione (GSH) levels in the acute group were also higher than in the hypertensive, chronic ischemic and control groups (p<0.05). The activity of AChE in acute ischemic patients was significantly higher than that presented by the control, hypertensive and chronic ischemic patients (p<0.05). The hypertensive group presented AChE activity significantly lower than control and chronic groups. In spite of having a defined location the ischemic event results in a systemic disorder that induces changes, which can be detected by measuring the peripheral markers of oxidative stress and AChE activity in erythrocytes.
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PMID:Oxidative stress and erythrocyte acetylcholinesterase (AChE) in hypertensive and ischemic patients of both acute and chronic stages. 1803 75

Present study was designed to investigate modulation of experimental dementia by Pitavastatin and donepezil. Learning and memory of the swiss albino mice were studied on Morris water-maze. Celecoxib orally (p.o.)/Streptozotocin (STZ) intracerebroventricular administrations were used to induce experimental dementia. Brain acetyl cholinesterase activity was measured by EllMann's method to assess cholinergic activity of the brain. Brain thio barbituric acid reactive species (TBARS) levels and reduced glutathione (GSH) levels were measured by Ohokawa's and Beutler's method respectively, to assess total oxidative stress in brain. Total serum cholesterol level was measured by Allain's method. Celecoxib/STZ treatments produced a significant loss of learning and memory. Pitavastatin/Donepezil successfully attenuated this Celecoxib/STZ induced dementia. Higher levels of brain acetyl-cholinesterase (AChE) activity, TBARS and lower level of GSH were observed in Celecoxib/STZ treated animals, which were significantly attenuated by Donepezil. Pitavastatin also attenuated the Celecoxib/STZ induced high levels of TBARS & low levels of GSH without effecting AChE activity and total serum cholesterol levels. Celecoxib induced dementia noted in the present study may be attributed to its stimulatory effect on amyloid beta-42, brain AChE activity, and oxidative stress. Sub-diabetogenic STZ induced memory deficits closely related to Alzheimer's disease. Reversal of Celecoxib/STZ induced memory deficits by Pitavastatin may be due to its antioxidative, anti beta amyloid aggregatory property, and by Donepezil, due to its anticholinesterase and neuroprotective actions.
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PMID:Modulation of celecoxib- and streptozotocin-induced experimental dementia of Alzheimer's disease by pitavastatin and donepezil. 1820 24

This study investigated lethal effects (i.e., survival) and sublethal effects (glutathione, GSH; lipid peroxidation, LPx; cholesterol, CHL; and acetylcholinesterase, AChE) of the antihyperlipidemic drug simvastatin on larval and adult grass shrimp (Palaemonetes pugio). The 96-h LC50 test for larvae resulted in an estimated LC50 of 1.18 mg/L (95% confidence interval 0.98-1.42 mg/L). The adult 96-h LC50 was >10.0 mg/L. GSH and AChE levels for both the larvae and the adults were not significantly affected by simvastatin exposure. LPx levels in the larvae were significantly higher than controls in the lowest and the highest simvastatin exposures. In adult grass shrimp, LPx levels were highest in the three lowest simvastatin exposures. CHL levels were significantly reduced in larvae at the highest simvastatin exposure level of 1 mg/L while adult CHL was not affected. Both lethal and sublethal effects associated with simvastatin exposure were only observed at concentrations well above those reported in the environment.
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PMID:Effects of the statin antihyperlipidemic agent simvastatin on grass shrimp, Palaemonetes pugio. 1821 20

Oxidative stress is a major factor implicated in the degeneration of cholinergic neurons in Alzheimer's disease. Presently, cholinesterase inhibitors are the mainstay of therapy for Alzheimer's disease. However, the potential of cholinesterase inhibitors as antioxidants, an important aspect for neuroprotection, has not been properly investigated. Therefore, the present study was designed to investigate the influence of antidementia drugs, tacrine and donepezil, on biochemical markers of oxidative stress, glutathione (GSH) and malondialdehyde (MDA), and acetylcholinesterase activity in the brain in a streptozotocin-induced experimental model of dementia in mice. Intracerebral (i.c.) injection of streptozotocin at a dose of 0.5 mg/kg on 1st and 3rd days caused significant deficits in memory function, as evaluated in a passive avoidance test and Morris Water Maze (spatial memory) test 14 days after the 1st dose. Mice were treated with tacrine and donepezil at a dose of 5 mg/kg orally in separate groups. Both tacrine- and donepezil-treated mice showed a significant improvement of the streptozotocin (i.c.)-induced memory impairment. Streptozotocin (i.c.) administration caused a significant decrease in GSH and increase in MDA as compared to control, indicating a state of oxidative stress in the brain of streptozotocin (i.c.) amnesic mice. Treatment of streptozotocin (i.c.) amnesic mice with tacrine or donepezil did not cause significant changes in GSH and MDA levels in the brain as compared to control. Streptozotocin amnesic mice had raised acetylcholinesterase activity in the brain while there was a significant decrease in brain acetylcholinesterase activity in tacrine- and donepezil-treated streptozotocin (i.c.) mice. Thus, results indicate that tacrine and donepezil, beside inhibition of acetylcholinesterase, may also suppress oxidative stress.
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PMID:Effect of donepezil and tacrine on oxidative stress in intracerebral streptozotocin-induced model of dementia in mice. 1823 83

The present study was undertaken to investigate the beneficial effect of HIV protease inhibitor Indinavir on memory deficits associated with experimental dementia of Alzheimer disease's (AD) type. Dementia was induced in Swiss albino mice by administration of Celecoxib (100 mg kg(-1) orally, daily for 9 days) or Streptozotocin (3 mg kg(-1) administered intracerebroventricularly on 1st and 3rd day) and the cognitive behaviors of Swiss albino mice were assessed using Morris water maze test. Brain acetyl cholinesterase (AChE) activity was measured by Ell Mann's method. Brain thiobarbituric acid reactive species (TBARS) levels and reduced glutathione (GSH) levels were measured by Ohokawa's and Beutler's method respectively to assess total oxidative stress. Donepezil (0.1 mg kg(-1) i.p.) served as positive control in the present investigation. Celecoxib as well as Streptozotocin (STZ) produced a significant loss of learning and memory. Indinavir (100 and 200 mg kg(-1) orally) successfully attenuated Celecoxib as well as STZ induced cognitive deficits. Higher levels of brain AChE activity, TBARS and lower levels of GSH were observed in Celecoxib as well as STZ treated animals, which were significantly attenuated by Donepezil and Indinavir. Study highlights the potential of Indinavir in memory dysfunctions associated with dementia of AD.
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PMID:Exploitation of HIV protease inhibitor Indinavir as a memory restorative agent in experimental dementia. 1834 89

This study examined the effects of a polybrominated diphenyl ether (PBDE) compound, PBDE-47, on adult and larval stages of the estuarine grass shrimp (Palaemonetes pugio). The 96-h LC50 test resulted in an estimate of 23.60 microg/L (95% confidence interval=14.51-38.37 microg/L) for larval shrimp. Adult shrimp had a higher 96-h LC50 of 78.07 microg/L (95% CI=65.1-93.63 microg/L). Four physiological biomarkers glutathione (GSH), lipid peroxidation (LPx), cholesterol (CHL) and acetylcholinesterase (AChE) were then assessed to study the sublethal effects of PBDE-47 exposure. GSH, LPx and AChE levels in both adults and larvae were not affected by PBDE-47 at concentrations up to 50 microg/L for 96 h. CHL levels were elevated in adults and larvae at the lowest exposure concentrations tested, but significant differences were found only in adult exposures. Effects associated with PBDE-47 aqueous exposures were observed at levels well above those reported in the environment.
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PMID:Toxicity and physiological effects of brominated flame retardant PBDE-47 on two life stages of grass shrimp, Palaemonetes pugio. 1845 54

The cognitive-enhancing activities of E-harpagoside and 8-O-E-p-methoxycinnamoylharpagide (MCA-Hg) isolated from Scrophularia buergeriana were evaluated in scopolamine-induced amnesic mice by the Morris water maze and by passive avoidance tests. E-harpagoside and MCA-Hg significantly improved the impairment of reference memory induced by scopolamine in the Morris water maze test. The mean escape latency, the mean path length and swimming movement were also improved by both compounds. In passive avoidance test, E-harpagoside and MCA-Hg (2 mg/kg body weight, p.o.) significantly ameliorated scopolamine-induced amnesia by as much as 70% of the level found in normal control mice. Donepezil, an acetylcholinesterase inhibitor and the most widely used drug for AD treatment was employed as a positive control. The activity of acetylcholinesterase was inhibited significantly by E-harpagoside or MCA-Hg within the cortex and hippocampus to a level similar to that observed in mice treated with donepezil (2 mg/kg body weight, p.o.). Moreover, treatment with E-harpagoside or MCA-Hg to scopolamine-induced amnesic mice significantly decreased TBARS level which was accompanied by an increase in the activities or contents of glutathione reductase, SOD and reduced GSH. We believe these data demonstrate that E-harpagoside or MCA-Hg exerted potent cognitive-enhancing activity through both anti-acetylcholinesterase and antioxidant mechanisms.
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PMID:Cognitive-enhancing and antioxidant activities of iridoid glycosides from Scrophularia buergeriana in scopolamine-treated mice. 1846 17

Azinphos-methyl is an organophosphate insecticide used for pest control on a number of food crops in many parts of the world. The oligochaete Lumbriculus variegatus and pigmented and non-pigmented specimens of the gastropod Biomphalaria glabrata are freshwater invertebrates that have been recommended for contamination studies. Recently, it has been shown that L. variegatus worms exhibit a higher cholinesterase (ChE) activity and a greater sensitivity to in vivo ChE inhibition by azinphos-methyl than pigmented B. glabrata snails. The aims of the present study were (1) to investigate if, in addition to its anticholinesterase action, azinphos-methyl has also pro-oxidant activity in L. variegatus and B. glabrata, and (2) to examine if species that are highly susceptible to the neurotoxic effects of organophosphates also suffer a greater degree of oxidative stress. Therefore, total glutathione (t-GSH) levels and activities of cholinesterase (ChE), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glucose 6-phosphate dehydrogenase (G6PDH) were measured in the whole body soft tissue of organisms exposed for 48 and 96 h to a level of azinphos-methyl that produces 50% of inhibition on ChE. Results showed different patterns of antioxidant responses between the gastropods and the oligochaetes, and even between the two phenotypes of gastropods: (1) in exposed L. variegatus t-GSH levels increased and CAT and SOD activities decreased with respect to control organisms, (2) in pigmented gastropods, SOD decreased while CAT transiently diminished, and (3) in non-pigmented gastropods, SOD activity showed a biphasic response. GST and G6PDH were not altered by azinphos-methyl exposure. Of note, t-GSH levels were 4-fold times higher in L. variegatus than in both phenotypes of B. glabrata. This may suggest that GSH could play a more important role in antioxidant defense in L. variegatus than in B. glabrata.
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PMID:Effects of azinphos-methyl exposure on enzymatic and non-enzymatic antioxidant defenses in Biomphalaria glabrata and Lumbriculus variegatus. 1853 25


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