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Naturally Occurring Acetylcholinesterase Inhibitors and Their Potential Use for Alzheimer's Disease Therapy.

TLDR
This mini-review aimed to recapitulate last decade studies on the anti-AChE activity of plant species, their respective extracts, as well as isolated compounds to help researchers out with the bioprospection of potentially new AChEi drugs.
Abstract
Alzheimer's disease (AD) is a main cause of dementia, accounting for up to 75% of all dementia cases. Pathophysiological processes described for AD progression involve neurons and synapses degeneration, mainly characterized by cholinergic impairment. This feature makes acetylcholinesterase inhibitors (AChEi) the main class of drugs currently used for the treatment of AD dementia phase, among which galantamine is the only naturally occurring substance. However, several plant species producing diverse classes of alkaloids, coumarins, terpenes, and polyphenols have been assessed for their anti-AChE activity, becoming potential candidates for new anti-AD drugs. Therefore, this mini-review aimed to recapitulate last decade studies on the anti-AChE activity of plant species, their respective extracts, as well as isolated compounds. The anti-AChE activity of extracts prepared from 54 plant species pertaining 29 families, as well as 36 isolated compounds were classified and discussed according to their anti-AChE pharmacological potency to highlight the most prominent ones. Besides, relevant limitations, such as proper antioxidant assessment, and scarcity of toxicological and clinical studies were also discussed in order to help researchers out with the bioprospection of potentially new AChEi.

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Journal ArticleDOI

Features and outcomes of drugs for combination therapy as multi-targets strategy to combat Alzheimer's disease.

TL;DR: An attempt has been made to elucidate the molecular mode of action of various plant products, and synthetic drugs investigated in various preclinical and clinical tests in AD, and discusses current attempts to formulate a comprehensive CDMT strategy to counter complex pathogenesis in AD.
Journal ArticleDOI

Icariin and Its Metabolites as Potential Protective Phytochemicals Against Alzheimer's Disease.

TL;DR: This mini-review discusses the multiple potential mechanisms of action of icariin on the pathobiology of AD including explanation regarding its bioavailability, metabolism and pharmacokinetic.
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Potent inhibition of acetylcholinesterase by sargachromanol I from Sargassum siliquastrum and by selected natural compounds

TL;DR: SCI, SCG, DB, and ML are suggested to be viewed as new reversible AChE inhibitors and useful lead compounds for the development for the treatment of Alzheimer's disease.
Journal ArticleDOI

Acetylcholinesterase inhibitors (nerve agents) as weapons of mass destruction: History, mechanisms of action, and medical countermeasures.

TL;DR: Treatment with diazepam or midazolam for the cessation of nerve agent-induced status epilepticus cannot protect against brain damage, and, therefore, these benzodiazepines should be replaced by novel anticonvulsants and neuroprotectants.
References
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Journal ArticleDOI

A new and rapid colorimetric determination of acetylcholinesterase activity.

TL;DR: A photometric method for determining acetylcholinesterase activity of tissue extracts, homogenates, cell suspensions, etc., has been described and Kinetic constants determined by this system for erythrocyte eholinesterases are presented.
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The Cholinergic Hypothesis of Geriatric Memory Dysfunction

TL;DR: Biochemical, electrophysiological, and pharmacological evidence supporting a role for cholinergic dysfunction in age-related memory disturbances is critically reviewed and an attempt has been made to identify pseudoissues, resolve certain controversies, and clarify misconceptions that have occurred in the literature.
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Acetylcholinesterase Inhibitors: Pharmacology and Toxicology

TL;DR: An overview of toxicology and pharmacology of reversible and irreversible acetylcholinesterase inactivating compounds is presented, with emphasis on oxime reactivators of the inhibited enzyme activity administering as causal drugs after the poisoning.
Journal ArticleDOI

On neurodegenerative diseases, models, and treatment strategies: lessons learned and lessons forgotten a generation following the cholinergic hypothesis.

TL;DR: A review of the current status of the cholinergic hypothesis in the context of continuing efforts to improve upon existing treatments for Alzheimer's disease and explores the role that animal models might continue to play as discussed by the authors.
Journal ArticleDOI

Acetylcholinesterase: From 3D structure to function

TL;DR: The crystal structure of recombinant human acetylcholinesterase in its apo-state is similar in its overall features to that of the Torpedo enzyme; however, the unique crystal packing reveals a novel peptide sequence which blocks access to the active-site gorge.
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