Acetylcholinesterase inhibitors as Alzheimer therapy: from nerve toxins to neuroprotection
Abstract
Acetylcholinesterase is a member of the α/β hydrolase protein super family, with a significant role in acetylcholine-mediated neurotransmission. Research in the modulators of AChEs has moved from a potent poison (Sarin, Soman) in war times to the potent medicine (physostigmine) in peaceful times. Natural anti-AChE includes carbamates, glycoalkaloids, anatoxins derived from green algae; synthetic anti-AChE includes highly poisonous organophosphates used as nerve gases and insecticides. Recently, the role of anti-AChE was reassessed from neurotoxins to neuron-protective in the diseases characterized by impaired acetylcholine-mediated neurotransmission like Alzheimer's disease (AD). So, the AChE has been proven to be the most viable therapeutic target for the symptomatic treatment of AD. This review article gives a spectrum of strategies to design AChE inhibitors used in the Alzheimer therapy.
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Acetylcholinesterase plays a role in the production of amyloid plaques and neurofibrillary tangles.
“In addition, the enzyme plays a role in the production of amyloid plaques and neurofibrillary tangles.”
From An update on the novel and approved drugs for Alzheimer disease (2022) · cites this paper as Singh et al., 2013
The positive effect of galantamine in restoring certain normal behavioral traits could result from its acetylcholinesterase inhibitor activity.
“the positive effect of galantamine in restoring certain normal behavioral traits could result from its acetylcholinesterase inhibitor activity.”
From Galantamine Slows Down Plaque Formation and Behavioral Decline in the 5XFAD Mouse Model of Alzheimer’s Disease (2014) · cites this paper as [54]
Acetylcholinesterase promotes the aggregation of β-amyloid peptide fragments by forming a complex with the growing fibrils.
“acetylcholinesterase has been shown to promote the aggregation of β-amyloid peptide fragments by forming a complex with the growing fibrils [54].”
From Galantamine Slows Down Plaque Formation and Behavioral Decline in the 5XFAD Mouse Model of Alzheimer’s Disease (2014) · cites this paper as [54]
According to the cholinergic hypothesis, decreased production of acetylcholine or amplified acetylcholinesterase activity results in impairment of cholinergic transmission, in turn leading to loss of intellectual abilities.
“According to the cholinergic hypothesis, a decreased production of acetylcholine or an amplified acetylcholinesterase activity results in impairment of the cholinergic transmission, in turn leading to the loss of intellectual abilities [54].”
From Galantamine Slows Down Plaque Formation and Behavioral Decline in the 5XFAD Mouse Model of Alzheimer’s Disease (2014) · cites this paper as [54]
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- Authors
- Singh, M., Kaur, M., Kukreja, H., Chugh, R., Silakari, O., & Singh, D.
- Affiliations
- Panjab University (IN)
- Corresponding author
- Singh, Dhandeep
- Venue
- European Journal of Medicinal Chemistry
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 70
- Pages
- 165-188
- ISSN
- 0223-5234 (ISSN-L)
- OpenAlex
- W1994264985
- Cited by
- 364
- References
- 210
- Citations by year
- 2026: 12 · 2025: 30 · 2024: 31 · 2023: 34 · 2022: 35 · 2021: 29 · 2020: 32 · 2019: 36 · 2018: 30 · 2017: 31 · 2016: 21 · 2015: 23 · 2014: 17 · 2013: 1
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
- Keywords
- acetylcholinesterase inhibitors, Alzheimer's disease, acetylcholinesterase, cholinergic neurotransmission, organophosphorus nerve agents, carbamate insecticides, physostigmine, glycoalkaloids, anatoxin, neuroprotection, drug design strategies, alpha/beta hydrolase superfamily
- MeSH terms
- Acetylcholinesterase, Alzheimer Disease, Animals, Cholinesterase Inhibitors, Humans, Drug Design, Molecular Structure
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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