Abstract
Alzheimer's Disease (AD) is a single major cause of dementia in middle to old age individuals involving several different etiopathological mechanisms that are yet to be properly characterized. Major invariant and characteristic features consist of the progressive cerebral deposition of the Amyloid β-protein (Aβ) and the neurofibrillary degeneration through Neurofibrillary Tangles (NFT) formed by hyperphosphorylation of the tau proteins in the regions of the brain that deal with memory and cognition. There are at least five subgroups of AD that can be identified by determining Cerebrospinal Fluid (CSF) levels of Aβ1-42, tau and ubiquitin. This multifactorial nature of the disease thus demands promising approaches for the development of rational disease-modifying drugs. A large number of agents have been discovered against individual targets but the success rate is very low and the number of compounds progressing to regulatory review is among the lowest found in any therapeutic area. A very promising modern approach solicits the design of Multi-Target-Directed Ligands (MTDLs) based on the “one molecule multiple targets” paradigm that has been specifically adopted for the treatment of disorders with complex pathological mechanisms. AD is one such disorder in which MTDL has found applicability. This review aims at providing an overview of the research carried out in discovering more efficient treatment against AD using MTDL, with a goal to ascertain safer drugs.
Keywords: MTDL, Multi-factorial, Secretase, Aβ aggregation, NFT, Anti-oxidant, Cholinesterase, MOA, PDE, APOE.
Current Topics in Medicinal Chemistry
Title:Multi-targeting Strategies for Alzheimer's Disease Therapeutics: Pros and Cons
Volume: 17 Issue: 27
Author(s): Sucharita Das and Soumalee Basu*
Affiliation:
- Department of Microbiology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata - 700 019,India
Keywords: MTDL, Multi-factorial, Secretase, Aβ aggregation, NFT, Anti-oxidant, Cholinesterase, MOA, PDE, APOE.
Abstract: Alzheimer's Disease (AD) is a single major cause of dementia in middle to old age individuals involving several different etiopathological mechanisms that are yet to be properly characterized. Major invariant and characteristic features consist of the progressive cerebral deposition of the Amyloid β-protein (Aβ) and the neurofibrillary degeneration through Neurofibrillary Tangles (NFT) formed by hyperphosphorylation of the tau proteins in the regions of the brain that deal with memory and cognition. There are at least five subgroups of AD that can be identified by determining Cerebrospinal Fluid (CSF) levels of Aβ1-42, tau and ubiquitin. This multifactorial nature of the disease thus demands promising approaches for the development of rational disease-modifying drugs. A large number of agents have been discovered against individual targets but the success rate is very low and the number of compounds progressing to regulatory review is among the lowest found in any therapeutic area. A very promising modern approach solicits the design of Multi-Target-Directed Ligands (MTDLs) based on the “one molecule multiple targets” paradigm that has been specifically adopted for the treatment of disorders with complex pathological mechanisms. AD is one such disorder in which MTDL has found applicability. This review aims at providing an overview of the research carried out in discovering more efficient treatment against AD using MTDL, with a goal to ascertain safer drugs.
Export Options
About this article
Cite this article as:
Das Sucharita and Basu Soumalee*, Multi-targeting Strategies for Alzheimer's Disease Therapeutics: Pros and Cons, Current Topics in Medicinal Chemistry 2017; 17 (27) . https://dx.doi.org/10.2174/1568026617666170707130652
DOI https://dx.doi.org/10.2174/1568026617666170707130652 |
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
-
Chemical Communication-Do We Have a Quorum?
Mini-Reviews in Medicinal Chemistry Stem Cells: In Sickness and in Health
Current Stem Cell Research & Therapy Preclinical Studies and Clinical Trials with Mesenchymal Stem Cell for Demyelinating Diseases: A Systematic Review
Current Stem Cell Research & Therapy PM6, PM7 and RM1 Quantum Chemistry Modeling of MEH-PPV and PEDOT Polymers
Current Physical Chemistry Berberine Administration in Treatment of Colitis: A Review
Current Drug Targets Clinical Applications of Non-Antimicrobial Actions of Tetracyclines in Inflammatory Diseases
Current Drug Therapy Problems in Statistical Analysis of Attrition in Randomized Controlled Clinical Trials of Antidepressant for Geriatric Depression
Current Psychiatry Reviews Meet Our Editorial Board Member:
Current Diabetes Reviews miRNAs in SARS-CoV 2: A Spoke in the Wheel of Pathogenesis
Current Pharmaceutical Design Progression of Alzheimer-type Neurofibrillary Tangles is Related to the Proximodistal Segments of the Hemispheric Arteries
Current Alzheimer Research Respiration and Energy Homeostasis
Current Respiratory Medicine Reviews Impact of Computational Structure-Based Predictive Toxicology in Drug Discovery
Combinatorial Chemistry & High Throughput Screening Protein/Polyphenol Interactions: Past and Present Contributions. Mechanisms of Astringency Perception
Current Organic Chemistry Targeting Glycogen Synthase Kinase-3 in the CNS: Implications for the Development of New Treatments for Mood Disorders
Current Drug Targets Obstructive Sleep Apnoea Syndrome and Diabetes. Fortuitous Association or Interaction?
Current Diabetes Reviews Gabapentin-Mediated Effects on Voltage- and Ligand-Gated Currents
Current Neuropharmacology Intravenous Application of Allogenic Peripheral Blood-Derived Mesenchymal Stem Cells: A Safety Assessment in 291 Equine Recipients
Current Stem Cell Research & Therapy Thoughts of Death, Depression and Guilt in a Healthcare Worker Who Infected Her Husband with SARS-CoV-2: A Case Report
CNS & Neurological Disorders - Drug Targets The Influence of Vaccine on Febrile Seizure
Current Neuropharmacology Magnetic Resonance Imaging of Short T2 Relaxation Components in Tissue Using Ultrashort Echo Time (UTE) Pulse Sequences
Current Medical Imaging