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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Unfolded Protein Response and PERK Kinase as a New Therapeutic Target in the Pathogenesis of Alzheimer’s Disease
Current Medicinal Chemistry The Development of Preventives and Therapeutics for Alzheimers Disease that Inhibit the Formation of β-Amyloid Fibrils (fAβ), as Well as Destabilize Preformed fAβ
Current Pharmaceutical Design Erythrocyte Amyloid Beta Peptide Isoform Distributions in Alzheimer and Mild Cognitive Impairment
Current Alzheimer Research The Multifactorial Nature of Alzheimer's Disease for Developing Potential Therapeutics
Current Topics in Medicinal Chemistry Association Studies of Sporadic Parkinson’s Disease in the Genomic Era
Current Genomics Principles and Therapeutic Relevance for Targeting Mitochondria in Aging and Neurodegenerative Diseases
Current Pharmaceutical Design Diuretic-Associated Electrolyte Disorders in the Elderly: Risk Factors, Impact, Management and Prevention
Current Drug Safety The Pleiotropic Effects of PPARs on Vascular Cells and Angiogenesis: Implications for Tissue Engineering
Current Stem Cell Research & Therapy Editorial (Thematic Issue: Treating Major Age-Related Diseases in Older and Oldest Old Patients)
Current Pharmaceutical Design Conference Report: The American Association for the Advancement of Science (AAAS), 180th Annual Meeting Chicago, IL, USA Feb 13-17, 2014 “Meeting Global Challenges: Discoveries & Innovation”
CNS & Neurological Disorders - Drug Targets NMR Structural Studies of Human Cellular Prion Proteins
Current Topics in Medicinal Chemistry Erythropoietin and Oxidative Stress
Current Neurovascular Research Recent Advances in Endocrine Metabolic Immune Disorders Drug Targeting: An Editorial Overview
Endocrine, Metabolic & Immune Disorders - Drug Targets Modulation of Monoaminergic Transporters by Choline-Containing Phospholipids in Rat Brain
CNS & Neurological Disorders - Drug Targets New Prospectives in the Delivery of Galantamine for Elderly Patients Using the IntelliDrug Intraoral Device: In Vivo Animal Studies
Current Pharmaceutical Design Anagliptin, A Dipeptidyl Peptidase-4 Inhibitor Ameliorates Arterial Stiffness in Association with Reduction of Remnant-Like Particle Cholesterol and Alanine Transaminase Levels in Type 2 Diabetic Patients
Current Vascular Pharmacology Visual Event-Related Potentials in Mild Cognitive Impairment and Alzheimer’s Disease: A Literature Review
Current Alzheimer Research Neuronal Cell Death in Alzheimers Disease and a Neuroprotective Factor, Humanin
Current Neuropharmacology Genetic Algorithm and Self-Organizing Maps for QSPR Study of Some N-aryl Derivatives as Butyrylcholinesterase Inhibitors
Current Drug Discovery Technologies Microglia-Neuron Interaction in Inflammatory and Degenerative Diseases: Role of Cholinergic and Noradrenergic Systems
CNS & Neurological Disorders - Drug Targets