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Advances in Multi-Functional Ligands and the Need for Metal-Related Pharmacology for the Management of Alzheimer Disease

Alzheimer’s disease (AD) is the age linked neurodegenerative disorder with no disease modifying therapy currently available. The available therapy only offers short term symptomatic relief. Several hypotheses have been suggested for the pathogenesis of the disease while the molecules developed as po...

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Autores principales: Sharma, Abha, Pachauri, Vidhu, Flora, S. J. S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249274/
https://www.ncbi.nlm.nih.gov/pubmed/30498443
http://dx.doi.org/10.3389/fphar.2018.01247
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author Sharma, Abha
Pachauri, Vidhu
Flora, S. J. S.
author_facet Sharma, Abha
Pachauri, Vidhu
Flora, S. J. S.
author_sort Sharma, Abha
collection PubMed
description Alzheimer’s disease (AD) is the age linked neurodegenerative disorder with no disease modifying therapy currently available. The available therapy only offers short term symptomatic relief. Several hypotheses have been suggested for the pathogenesis of the disease while the molecules developed as possible therapeutic agent in the last decade, largely failed in the clinical trials. Several factors like tau protein hyperphosphorylation, amyloid-β (Aβ) peptide aggregation, decline in acetyl cholinesterase and oxidative stress might be contributing toward the pathogenesis of AD. Additionally, biometals dyshomeostasis (Iron, Copper, and Zinc) in the brain are also reported to be involved in the pathogenesis of AD. Thus, targeting these metal ions may be an effective strategy for the development of a drug to treat AD. Chelation therapy is currently employed for the metal intoxication but we lack a safe and effective chelating agents with additional biological properties for their possible use as multi target directed ligands for a complex disease like AD. Chelating agents possess the ability to disaggregate Aβ aggregation, dissolve amyloid plaques, and delay the cognitive impairment. Thus there is an urgent need to develop disease modifying therapeutic molecules with multiple beneficial features like targeting more than one factor responsible of the disease. These molecules, as disease modifying therapeutic agents for AD, should possess the potential to inhibit Aβ-metal interactions, the formation of toxic Aβ aggregates; and the capacity to reinstate metal homeostasis.
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spelling pubmed-62492742018-11-29 Advances in Multi-Functional Ligands and the Need for Metal-Related Pharmacology for the Management of Alzheimer Disease Sharma, Abha Pachauri, Vidhu Flora, S. J. S. Front Pharmacol Pharmacology Alzheimer’s disease (AD) is the age linked neurodegenerative disorder with no disease modifying therapy currently available. The available therapy only offers short term symptomatic relief. Several hypotheses have been suggested for the pathogenesis of the disease while the molecules developed as possible therapeutic agent in the last decade, largely failed in the clinical trials. Several factors like tau protein hyperphosphorylation, amyloid-β (Aβ) peptide aggregation, decline in acetyl cholinesterase and oxidative stress might be contributing toward the pathogenesis of AD. Additionally, biometals dyshomeostasis (Iron, Copper, and Zinc) in the brain are also reported to be involved in the pathogenesis of AD. Thus, targeting these metal ions may be an effective strategy for the development of a drug to treat AD. Chelation therapy is currently employed for the metal intoxication but we lack a safe and effective chelating agents with additional biological properties for their possible use as multi target directed ligands for a complex disease like AD. Chelating agents possess the ability to disaggregate Aβ aggregation, dissolve amyloid plaques, and delay the cognitive impairment. Thus there is an urgent need to develop disease modifying therapeutic molecules with multiple beneficial features like targeting more than one factor responsible of the disease. These molecules, as disease modifying therapeutic agents for AD, should possess the potential to inhibit Aβ-metal interactions, the formation of toxic Aβ aggregates; and the capacity to reinstate metal homeostasis. Frontiers Media S.A. 2018-11-15 /pmc/articles/PMC6249274/ /pubmed/30498443 http://dx.doi.org/10.3389/fphar.2018.01247 Text en Copyright © 2018 Sharma, Pachauri and Flora. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Sharma, Abha
Pachauri, Vidhu
Flora, S. J. S.
Advances in Multi-Functional Ligands and the Need for Metal-Related Pharmacology for the Management of Alzheimer Disease
title Advances in Multi-Functional Ligands and the Need for Metal-Related Pharmacology for the Management of Alzheimer Disease
title_full Advances in Multi-Functional Ligands and the Need for Metal-Related Pharmacology for the Management of Alzheimer Disease
title_fullStr Advances in Multi-Functional Ligands and the Need for Metal-Related Pharmacology for the Management of Alzheimer Disease
title_full_unstemmed Advances in Multi-Functional Ligands and the Need for Metal-Related Pharmacology for the Management of Alzheimer Disease
title_short Advances in Multi-Functional Ligands and the Need for Metal-Related Pharmacology for the Management of Alzheimer Disease
title_sort advances in multi-functional ligands and the need for metal-related pharmacology for the management of alzheimer disease
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249274/
https://www.ncbi.nlm.nih.gov/pubmed/30498443
http://dx.doi.org/10.3389/fphar.2018.01247
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