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An Overview of Several Inhibitors for Alzheimer’s Disease: Characterization and Failure
Amyloid beta (Aβ) oligomers are the most neurotoxic aggregates causing neuronal death and cognitive damage. A detailed elucidation of the aggregation pathways from oligomers to fibril formation is crucial to develop therapeutic strategies for Alzheimer’s disease (AD). Although experimental technique...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509255/ https://www.ncbi.nlm.nih.gov/pubmed/34639140 http://dx.doi.org/10.3390/ijms221910798 |
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author | Boopathi, Subramanian Poma, Adolfo B. Garduño-Juárez, Ramón |
author_facet | Boopathi, Subramanian Poma, Adolfo B. Garduño-Juárez, Ramón |
author_sort | Boopathi, Subramanian |
collection | PubMed |
description | Amyloid beta (Aβ) oligomers are the most neurotoxic aggregates causing neuronal death and cognitive damage. A detailed elucidation of the aggregation pathways from oligomers to fibril formation is crucial to develop therapeutic strategies for Alzheimer’s disease (AD). Although experimental techniques rely on the measure of time- and space-average properties, they face severe difficulties in the investigation of Aβ peptide aggregation due to their intrinsically disorder character. Computer simulation is a tool that allows tracing the molecular motion of molecules; hence it complements Aβ experiments, as it allows to explore the binding mechanism between metal ions and Aβ oligomers close to the cellular membrane at the atomic resolution. In this context, integrated studies of experiments and computer simulations can assist in mapping the complete pathways of aggregation and toxicity of Aβ peptides. Aβ oligomers are disordered proteins, and due to a rapid exploration of their intrinsic conformational space in real-time, they are challenging therapeutic targets. Therefore, no good drug candidate could have been identified for clinical use. Our previous investigations identified two small molecules, M30 (2-Octahydroisoquinolin-2(1H)-ylethanamine) and Gabapentin, capable of Aβ binding and inhibiting molecular aggregation, synaptotoxicity, intracellular calcium signaling, cellular toxicity and memory losses induced by Aβ. Thus, we recommend these molecules as novel candidates to assist anti-AD drug discovery in the near future. This review discusses the most recent research investigations about the Aβ dynamics in water, close contact with cell membranes, and several therapeutic strategies to remove plaque formation. |
format | Online Article Text |
id | pubmed-8509255 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85092552021-10-13 An Overview of Several Inhibitors for Alzheimer’s Disease: Characterization and Failure Boopathi, Subramanian Poma, Adolfo B. Garduño-Juárez, Ramón Int J Mol Sci Review Amyloid beta (Aβ) oligomers are the most neurotoxic aggregates causing neuronal death and cognitive damage. A detailed elucidation of the aggregation pathways from oligomers to fibril formation is crucial to develop therapeutic strategies for Alzheimer’s disease (AD). Although experimental techniques rely on the measure of time- and space-average properties, they face severe difficulties in the investigation of Aβ peptide aggregation due to their intrinsically disorder character. Computer simulation is a tool that allows tracing the molecular motion of molecules; hence it complements Aβ experiments, as it allows to explore the binding mechanism between metal ions and Aβ oligomers close to the cellular membrane at the atomic resolution. In this context, integrated studies of experiments and computer simulations can assist in mapping the complete pathways of aggregation and toxicity of Aβ peptides. Aβ oligomers are disordered proteins, and due to a rapid exploration of their intrinsic conformational space in real-time, they are challenging therapeutic targets. Therefore, no good drug candidate could have been identified for clinical use. Our previous investigations identified two small molecules, M30 (2-Octahydroisoquinolin-2(1H)-ylethanamine) and Gabapentin, capable of Aβ binding and inhibiting molecular aggregation, synaptotoxicity, intracellular calcium signaling, cellular toxicity and memory losses induced by Aβ. Thus, we recommend these molecules as novel candidates to assist anti-AD drug discovery in the near future. This review discusses the most recent research investigations about the Aβ dynamics in water, close contact with cell membranes, and several therapeutic strategies to remove plaque formation. MDPI 2021-10-06 /pmc/articles/PMC8509255/ /pubmed/34639140 http://dx.doi.org/10.3390/ijms221910798 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Boopathi, Subramanian Poma, Adolfo B. Garduño-Juárez, Ramón An Overview of Several Inhibitors for Alzheimer’s Disease: Characterization and Failure |
title | An Overview of Several Inhibitors for Alzheimer’s Disease: Characterization and Failure |
title_full | An Overview of Several Inhibitors for Alzheimer’s Disease: Characterization and Failure |
title_fullStr | An Overview of Several Inhibitors for Alzheimer’s Disease: Characterization and Failure |
title_full_unstemmed | An Overview of Several Inhibitors for Alzheimer’s Disease: Characterization and Failure |
title_short | An Overview of Several Inhibitors for Alzheimer’s Disease: Characterization and Failure |
title_sort | overview of several inhibitors for alzheimer’s disease: characterization and failure |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509255/ https://www.ncbi.nlm.nih.gov/pubmed/34639140 http://dx.doi.org/10.3390/ijms221910798 |
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