Abstract
The therapeutic arsenal for the treatment of Alzheimers disease (AD) remains confined to a group of four inhibitors of AChE and one NMDA receptor antagonist, which are used to provide a relief of the very late symptoms of the dementia, i.e. the cognitive and functional decline. In line with the growing body of evidence of the pivotal role of the β-amyloid peptide (Aβ) in the pathogenesis of AD, alternative classes of drugs targeting mainly the formation or the aggregation of Aβ are actively pursued by the pharmaceutical industry, as they could positively modify the course of AD, stopping or slowing down disease progression. While the first amyloid-directed disease-modifying drugs go ahead with their clinical development and could reach the market as soon as 2009, mounting preclinical and clinical evidences is pointing towards a disease-modifying role also for currently marketed anti-Alzheimer AChE inhibitors (AChEIs), particularly for donepezil. In this review, the neuroprotective effects exhibited by currently commercialized AChEIs will be briefly discussed, together with the secondary mechanisms through which they could exert such effects. This review will focus also on particular classes of AChEIs, namely dual binding site AChEIs, which are being purposely designed to target Aβ aggregation and / or other biological targets that contribute to AD pathogenesis, thus constituting very promising diseasemodifying anti-Alzheimer drug candidates.
Keywords: Disease-modifying anti-Alzheimer drugs, neuroprotection, Aβ aggregation, dual site binding, multifunctional drugs
Current Medicinal Chemistry
Title: Acetylcholinesterase Inhibitors as Disease-Modifying Therapies for Alzheimers Disease
Volume: 15 Issue: 24
Author(s): D. Munoz-Torrero
Affiliation:
Keywords: Disease-modifying anti-Alzheimer drugs, neuroprotection, Aβ aggregation, dual site binding, multifunctional drugs
Abstract: The therapeutic arsenal for the treatment of Alzheimers disease (AD) remains confined to a group of four inhibitors of AChE and one NMDA receptor antagonist, which are used to provide a relief of the very late symptoms of the dementia, i.e. the cognitive and functional decline. In line with the growing body of evidence of the pivotal role of the β-amyloid peptide (Aβ) in the pathogenesis of AD, alternative classes of drugs targeting mainly the formation or the aggregation of Aβ are actively pursued by the pharmaceutical industry, as they could positively modify the course of AD, stopping or slowing down disease progression. While the first amyloid-directed disease-modifying drugs go ahead with their clinical development and could reach the market as soon as 2009, mounting preclinical and clinical evidences is pointing towards a disease-modifying role also for currently marketed anti-Alzheimer AChE inhibitors (AChEIs), particularly for donepezil. In this review, the neuroprotective effects exhibited by currently commercialized AChEIs will be briefly discussed, together with the secondary mechanisms through which they could exert such effects. This review will focus also on particular classes of AChEIs, namely dual binding site AChEIs, which are being purposely designed to target Aβ aggregation and / or other biological targets that contribute to AD pathogenesis, thus constituting very promising diseasemodifying anti-Alzheimer drug candidates.
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Cite this article as:
Munoz-Torrero D., Acetylcholinesterase Inhibitors as Disease-Modifying Therapies for Alzheimers Disease, Current Medicinal Chemistry 2008; 15 (24) . https://dx.doi.org/10.2174/092986708785909067
DOI https://dx.doi.org/10.2174/092986708785909067 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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