Abstract
Notwithstanding the functional role that the aggregates of some amyloidogenic proteins can play in different organisms, protein aggregation plays a pivotal role in the pathogenesis of a large number of human diseases. One of such diseases is Alzheimer’s disease (AD), where the overproduction and aggregation of the β-amyloid peptide (Aβ) are regarded as early critical factors. Another protein that seems to occupy a prominent position within the complex pathological network of AD is the enzyme acetylcholinesterase (AChE), with classical and non-classical activities involved at the late (cholinergic deficit) and early (Aβ aggregation) phases of the disease. Dual inhibitors of Aβ aggregation and AChE are thus emerging as promising multi-target agents with potential to efficiently modify the natural course of AD. In the initial phases of the drug discovery process of such compounds, in vitro evaluation of the inhibition of Aβ aggregation is rather troublesome, as it is very sensitive to experimental assay conditions, and requires expensive synthetic Aβ peptides, which makes cost-prohibitive the screening of large compound libraries. Herein, we review recently developed multitarget anti-Alzheimer compounds that exhibit both Aβ aggregation and AChE inhibitory activities, and, in some cases also additional valuable activities such as BACE-1 inhibition or antioxidant properties. We also discuss the development of simplified in vivo methods for the rapid, simple, reliable, unexpensive, and high-throughput amenable screening of Aβ aggregation inhibitors that rely on the overexpression of Aβ42 alone or fused with reporter proteins in Escherichia coli.
Keywords: Aggregation, Alzheimer’s disease, amyloid, bacterial inclusion bodies, dual inhibitors, in vivo assays.
Current Topics in Medicinal Chemistry
Title:Dual Inhibitors of β-Amyloid Aggregation and Acetylcholinesterase as Multi-Target Anti-Alzheimer Drug Candidates
Volume: 13 Issue: 15
Author(s): Elisabet Viayna, Raimon Sabate and Diego Muñoz-Torrero
Affiliation:
Keywords: Aggregation, Alzheimer’s disease, amyloid, bacterial inclusion bodies, dual inhibitors, in vivo assays.
Abstract: Notwithstanding the functional role that the aggregates of some amyloidogenic proteins can play in different organisms, protein aggregation plays a pivotal role in the pathogenesis of a large number of human diseases. One of such diseases is Alzheimer’s disease (AD), where the overproduction and aggregation of the β-amyloid peptide (Aβ) are regarded as early critical factors. Another protein that seems to occupy a prominent position within the complex pathological network of AD is the enzyme acetylcholinesterase (AChE), with classical and non-classical activities involved at the late (cholinergic deficit) and early (Aβ aggregation) phases of the disease. Dual inhibitors of Aβ aggregation and AChE are thus emerging as promising multi-target agents with potential to efficiently modify the natural course of AD. In the initial phases of the drug discovery process of such compounds, in vitro evaluation of the inhibition of Aβ aggregation is rather troublesome, as it is very sensitive to experimental assay conditions, and requires expensive synthetic Aβ peptides, which makes cost-prohibitive the screening of large compound libraries. Herein, we review recently developed multitarget anti-Alzheimer compounds that exhibit both Aβ aggregation and AChE inhibitory activities, and, in some cases also additional valuable activities such as BACE-1 inhibition or antioxidant properties. We also discuss the development of simplified in vivo methods for the rapid, simple, reliable, unexpensive, and high-throughput amenable screening of Aβ aggregation inhibitors that rely on the overexpression of Aβ42 alone or fused with reporter proteins in Escherichia coli.
Export Options
About this article
Cite this article as:
Viayna Elisabet, Sabate Raimon and Muñoz-Torrero Diego, Dual Inhibitors of β-Amyloid Aggregation and Acetylcholinesterase as Multi-Target Anti-Alzheimer Drug Candidates, Current Topics in Medicinal Chemistry 2013; 13 (15) . https://dx.doi.org/10.2174/15680266113139990139
DOI https://dx.doi.org/10.2174/15680266113139990139 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Integrative Analysis of miRNA-mediated Competing Endogenous RNA Network Reveals the lncRNAs-mRNAs Interaction in Glioblastoma Stem Cell Differentiation
Current Bioinformatics Unsupervised End-to-End Brain Tumor Magnetic Resonance Image Registration Using RBCNN: Rigid Transformation, B-Spline Transformation and Convolutional Neural Network
Current Medical Imaging Circulating Tumor Stem Cells as Biomarkers for Cancer Progression
Recent Patents on Biomarkers Calcium Ion – The Key Player in Cerebral Ischemia
Current Medicinal Chemistry Regulation of the PI3K-Akt Network: Current Status and a Promise for the Treatment of Human Diseases
Current Signal Transduction Therapy Pisosterol Induces G2/M Cell Cycle Arrest and Apoptosis via the ATM/ATR Signaling Pathway in Human Glioma Cells
Anti-Cancer Agents in Medicinal Chemistry Physiopathological Roles of P2X Receptors in the Central Nervous System
Current Medicinal Chemistry Newer Insights in Personalized and Evidence Based Medicine- the Role of MicroRNAs
Current Pharmacogenomics and Personalized Medicine The Interaction of Histone Deacetylase Inhibitors and DNA Methyltransferase Inhibitors in the Treatment of Human Cancer Cells
Current Medicinal Chemistry - Anti-Cancer Agents 2-Methoxyestradiol as a Potential Cytostatic Drug in Gliomas?
Anti-Cancer Agents in Medicinal Chemistry Synthesis and Bioactivity of (R)-Ricinoleic Acid Derivatives: A Review
Current Medicinal Chemistry Synthesis of (R)-2-benzylmorpholine employing catalytic stereospecific rearrangement of L-Phenylalaninol
Letters in Organic Chemistry Brain Targeted Drug Delivery: Factors, Approaches and Patents
Recent Patents on Nanomedicine Mechanisms and Inhibitors of Apoptosis in Cardiovascular Diseases
Current Pharmaceutical Design Current Progresses in Metal-based Anticancer Complexes as Mammalian TrxR Inhibitors
Anti-Cancer Agents in Medicinal Chemistry Mammalian Target of Rapamycin (mTOR) Inhibitors as Anti-Cancer Agents
Current Cancer Drug Targets Cannabinoids as Neuroprotective Agents in Traumatic Brain Injury
Current Pharmaceutical Design Gene Therapy and Cell Reprogramming For the Aging Brain: Achievements and Promise
Current Gene Therapy Microglia Phenotype Diversity
CNS & Neurological Disorders - Drug Targets Near-infrared Light Activatable Multimodal Gold Nanostructures Platform: An Emerging Paradigm for Cancer Therapy
Current Cancer Drug Targets