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)

Amyloid beta protein (Abeta) may be neurotoxic during the progression of Alzheimer's disease by eliciting oxidative stress. This study was designed to determine the effect of Polygonum multiflorum Thunb water extract (PWE) on Abeta25-35-induced cognitive deficits and oxidative stress in mice. Mice were fed experimental diets comprising either 0.5 or 1% PWE for 4 weeks, and then received a single intracerebroventricular (i.c.v.) injection of Abeta25-35 (10 microg/mouse). Behavioral changes in the mice were evaluated using passive avoidance and water-maze tests. The consumption of PWE significantly ameliorated the cognitive deficits caused by i.c.v. injection of Abeta25-35. The Abeta25-35 treatment accelerated the lipid peroxidation, and PWE attenuated the Abeta-induced increase in brain levels of thiobarbituric acid reactive substances. There was an increase in glutathione peroxidase activity in PWE-treated groups. The acetylcholinesterase activity in the brain and serum was lower in PWE supplemented groups than in the only Abeta-injected group. These findings suggest that PWE exerts a preventive effect against cognitive deficits induced by Abeta25-35 accumulation in Alzheimer's disease, and that this effect is mediated by the antioxidant properties of PWE.
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PMID:Protective effect of Polygonum multiflorum Thunb on amyloid beta-peptide 25-35 induced cognitive deficits in mice. 1621 38

Major characteristics of Alzheimer's disease (AD) are synaptic loss, cholinergic dysfunction, and abnormal protein depositions in the brain. The amyloid beta-peptide (Abeta), a proteolytic fragment of amyloid beta precursor protein (APP), aggregates to form neuritic plaques and has a causative role in AD. A present focus of AD research is to develop safe Abeta-lowering drugs. A selective acetylcholinesterase inhibitor, phenserine, in current human trials lowers both APP and Abeta. Phenserine is dose-limited in animals by its cholinergic actions; its cholinergically inactive enantiomer, posiphen (+)-[phenserine], was assessed. In cultured human neuroblastoma cells, posiphen, like phenserine, dose- and time-dependently lowered APP and Abeta levels by reducing the APP synthesis rate. This action translated to an in vivo system. Posiphen administration to mice (7.5-75 mg/kg daily, 21 consecutive days) significantly decreased levels of total APP (tissue mass-adjusted) in a dose-dependent manner. Abeta40 and Abeta42 levels were significantly lowered by posiphen (> or =15 mg/kg) compared with controls. The activities of alpha-, beta-, and gamma-secretases were assessed in the same brain samples, and beta-secretase activity was significantly reduced. Posiphen, like phenserine, can lower Abeta via multiple mechanisms and represents an interesting drug candidate for AD treatment.
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PMID:The experimental Alzheimer's disease drug posiphen [(+)-phenserine] lowers amyloid-beta peptide levels in cell culture and mice. 1700 27