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
-
Pharmacological Strategies to Increase the Antitumor Activity of Methylating Agents
Current Medicinal Chemistry SDResU-Net: Separable and Dilated Residual U-Net for MRI Brain Tumor Segmentation
Current Medical Imaging Inhibitor at the Gates, Inhibitor in the Chamber: Allosteric and Competitive Inhibitors of the Proteasome as Prospective Drugs
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents The Role of 3D Pharmacophore Mapping Based Virtual Screening for Identification of Novel Anticancer Agents: An Overview
Current Topics in Medicinal Chemistry Nanocarriers for Anticancer Drugs - New Trends in Nanomedicine
Current Drug Metabolism Novel Gastrin Receptor-Directed Contrast Agents - Potential in Brain Tumor Magnetic Resonance Imaging
Medicinal Chemistry Membrane Interacting Peptides: A Review
Current Protein & Peptide Science Carbonic Anhydrase Inhibitors as Anticonvulsant Agents
Current Topics in Medicinal Chemistry Nanoparticle-based Drug Delivery Systems for Solid Brain Tumors
Current Nanoscience Personalizing Stem Cell Research and Therapy: The Arduous Road Ahead or Missed Opportunity?
Current Pharmacogenomics and Personalized Medicine Graphical Abstracts:
Central Nervous System Agents in Medicinal Chemistry Application of NMR Spectroscopy in Medicinal Chemistry and Drug Discovery
Current Topics in Medicinal Chemistry Major Developments in the Design of Inhibitors along the Kynurenine Pathway
Current Medicinal Chemistry Role of the APP Non-Amyloidogenic Signaling Pathway and Targeting α-Secretase as an Alternative Drug Target for Treatment of Alzheimers Disease
Current Medicinal Chemistry Polycation-Based Gene Therapy: Current Knowledge and New Perspectives
Current Gene Therapy Advanced Techniques for Imaging the Human Spinal Cord: Review of Literature
Current Medical Imaging Double Layered Hydroxides as Potential Anti-Cancer Drug Delivery Agents
Mini-Reviews in Medicinal Chemistry Vagotomy and Gastric Tumorigenesis
Current Neuropharmacology Targeting RANK/RANKL in the Treatment of Solid Tumours and Myeloma
Current Pharmaceutical Design Meet the Editorial Board:
Current Alzheimer Research