Abstract
Although the hallmarks of neurodegeneration in Alzheimers 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 Alzheimers 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 β-amyloid (Aβ). AChE could play a role in the Aβ metabolism and during an early step in the development of the senile plaque, as revealed by the finding that AChE accelerates Ab 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 Aβ 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 Ab 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 Alzheimers disease.
Keywords: Beta-amyloid aggregation, dual binding site acetylcholinesterase inhibitors, peripheral site
Current Pharmaceutical Design
Title: Targeting Beta-Amyloid Pathogenesis Through Acetylcholinesterase Inhibitors
Volume: 12 Issue: 33
Author(s): Ana Castro and Ana Martinez
Affiliation:
Keywords: Beta-amyloid aggregation, dual binding site acetylcholinesterase inhibitors, peripheral site
Abstract: Although the hallmarks of neurodegeneration in Alzheimers 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 Alzheimers 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 β-amyloid (Aβ). AChE could play a role in the Aβ metabolism and during an early step in the development of the senile plaque, as revealed by the finding that AChE accelerates Ab 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 Aβ 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 Ab 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 Alzheimers disease.
Export Options
About this article
Cite this article as:
Castro Ana and Martinez Ana, Targeting Beta-Amyloid Pathogenesis Through Acetylcholinesterase Inhibitors, Current Pharmaceutical Design 2006; 12 (33) . https://dx.doi.org/10.2174/138161206778792985
DOI https://dx.doi.org/10.2174/138161206778792985 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Unequivocal Role of Pyrazine Ring in Medicinally Important Compounds: A Review
Mini-Reviews in Medicinal Chemistry Berberine: A Plant-derived Alkaloid with Therapeutic Potential to Combat Alzheimer’s disease
Central Nervous System Agents in Medicinal Chemistry A Neuroinformatics Study Describing Molecular Interaction of Cisplatin with Acetylcholinesterase: A Plausible Cause for Anticancer Drug Induced Neurotoxicity
CNS & Neurological Disorders - Drug Targets Therapeutic Use of Molecules that Mimic Pathogen Danger Signals
Endocrine, Metabolic & Immune Disorders - Drug Targets A Quantitative Proteomic Analysis to Reveal Effects of N-acetylcysteine on H<sub>2</sub>O<sub>2</sub>-induced Cytotoxicity
Current Proteomics Interventional Radiology in Paediatrics
Current Pediatric Reviews Targeting βIII-Tubulin in Glioblastoma Multiforme: From Cell Biology and Histopathology to Cancer Therapeutics
Anti-Cancer Agents in Medicinal Chemistry Calcium-Sensing Receptor (CaSR) in Human Brains Pathophysiology: Roles in Late-Onset Alzheimers Disease (LOAD)
Current Pharmaceutical Biotechnology P53 Family: At the Crossroads in Cancer Therapy
Current Medicinal Chemistry Multivariate Statistical Tools for the Evaluation of Proteomic 2D-maps:Recent Achievements and Applications
Current Proteomics Iodine in Mammary and Prostate Pathologies
Current Chemical Biology Confocal Microscopy Evidence of Prion Protein Fragment hPrP[173-195] Internalization in Rat B104 Neuroblastoma Cell Line
Protein & Peptide Letters Role of Autophagy in Alzheimer’s Disease
Current Enzyme Inhibition Hydrogen Sulphide: Biopharmacological Roles in the Cardiovascular System and Pharmaceutical Perspectives
Current Medicinal Chemistry Interplay between DNA Methyltransferase 1 and microRNAs During Tumorigenesis
Current Drug Targets On the Physiological Role of Cytosolic 5’-nucleotidase II (cN-II): Pathological and Therapeutical Implications.
Current Medicinal Chemistry α7 Nicotinic Acetylcholine Receptors in Alzheimer’s Disease: Neuroprotective, Neurotrophic or Both?
Current Drug Targets Toward The Rational Design of Cell Fate Modifiers Notch Signaling as a Target for Novel Biopharmaceuticals
Current Pharmaceutical Biotechnology Beta-Caryophyllene, a CB2R Selective Agonist, Protects Against Cognitive Impairment Caused by Neuro-inflammation and Not in Dementia Due to Ageing Induced by Mitochondrial Dysfunction
CNS & Neurological Disorders - Drug Targets Mechanism-based Modulator Discovery for Sirtuin-catalyzed Deacetylation Reaction
Mini-Reviews in Medicinal Chemistry