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Targeting Beta-Amyloid Pathogenesis Through Acetylcholinesterase Inhibitors
Abstract
Although the hallmarks of neurodegeneration in Alzheimer's brains are well known, one of the current difficulties is related to the lack of solid evidence about the ultimate factors that give rise to the pathogenesis of this disease, creating a great challenge for the definition of efficient treatments for Alzheimer's disease (AD). Current therapeutic option for AD patients is the use of acetylcholinesterase (AChE) inhibitors, which gives only a symptomatic relief. However, recent studies show a long-lasting effect in a certain percentage of patients. In fact, there is accumulating evidence that an AChE has secondary non-cholinergic functions including the processing and deposition of beta-amyloid (Abeta). AChE could play a role in the Abeta metabolism and during an early step in the development of the senile plaque, as revealed by the finding that AChE accelerates Abeta deposition. Considering the non-classical AChE functions, their relationships with AD hallmarks, and the putative role of peripheral anionic site in all these functions, the dual binding site AChE inhibitors may acquire importance for AD treatment. On the other hand, the interference of AChE inhibitors with Abeta processing is not a general rule for this class of compounds with the involvement of other features such as chemical structure and/or genetic regulation. This review highlights the collection of several compounds with an outstanding profile against AChE-induced amyloid aggregation and potent AChE inhibitory activity, indicating the possibility of targeting Abeta through the inhibition of AChE and reveals the emergence of a new generation of AChE inhibitors aiming to be excellent candidate drugs for the future cure of Alzheimer's disease.
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“Moreover, the conformational changes due to AChE-Aβ complex formation also enhanced the metabolism of Aβ and senile plaque generation [30].”
From Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy (2021) · cites this paper as [30]
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Metadata
- Authors
- Castro, A., & Martinez, A.
- ORCID
- Castro, Ana
- Venue
- Current Pharmaceutical Design
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2006-11-01
- Volume
- 12
- Issue
- 33
- Pages
- 4377-4387
- ISSN
- 1381-6128 (ISSN-L)
- OpenAlex
- W1976042714
- Cited by
- 207
- References
- 75
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 12 · 2023: 7 · 2022: 13 · 2021: 13 · 2020: 12 · 2019: 10 · 2018: 7 · 2017: 16 · 2016: 16 · 2015: 11 · 2014: 9 · 2013: 8 · 2012: 15
- FWCI
- 5.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Pharmaceutical Design (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme function and inhibition
- Keywords
- Alzheimer's disease, amyloid-beta, acetylcholinesterase inhibitors, amyloid fibril formation, peripheral anionic site, dual binding site inhibitors, amyloid plaques, amyloid deposition
- MeSH terms
- Alzheimer Disease, Cholinesterase Inhibitors, Humans, Amyloid beta-Peptides
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