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Rosmarinic acid prevents fibrillization and diminishes vibrational modes associated to β sheet in tau protein linked to Alzheimer’s disease
Alzheimer’s disease is a common tauopathy where fibril formation and aggregates are the hallmark of the disease. Efforts targeting amyloid-β plaques have succeeded to remove plaques but failed in clinical trials to improve cognition; thus, the current therapeutic strategy is at preventing tau aggreg...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009890/ https://www.ncbi.nlm.nih.gov/pubmed/28701064 http://dx.doi.org/10.1080/14756366.2017.1347783 |
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author | Cornejo, Alberto Aguilar Sandoval, Felipe Caballero, Leonardo Machuca, Luis Muñoz, Patricio Caballero, Julio Perry, George Ardiles, Alejandro Areche, Carlos Melo, Francisco |
author_facet | Cornejo, Alberto Aguilar Sandoval, Felipe Caballero, Leonardo Machuca, Luis Muñoz, Patricio Caballero, Julio Perry, George Ardiles, Alejandro Areche, Carlos Melo, Francisco |
author_sort | Cornejo, Alberto |
collection | PubMed |
description | Alzheimer’s disease is a common tauopathy where fibril formation and aggregates are the hallmark of the disease. Efforts targeting amyloid-β plaques have succeeded to remove plaques but failed in clinical trials to improve cognition; thus, the current therapeutic strategy is at preventing tau aggregation. Here, we demonstrated that four phenolic diterpenoids and rosmarinic acid inhibit fibrillization. Since, rosmarinic acid was the most active compound, we observe morphological changes in atomic force microscopy images after treatment. Hence, rosmarinic acid leads to a decrease in amide regions I and III, indicating that rosmarinic acid prevents β-sheet assembly. Molecular docking study inside the steric zipper model of the hexapeptide (306)VQIVYK(311) involved in fibrillization and β sheet formation, suggests that rosmarinic acid binds to the steric zipper with similar chemical interactions with respect to those observed for orange G, a known pharmacofore for amyloid. |
format | Online Article Text |
id | pubmed-6009890 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-60098902018-07-11 Rosmarinic acid prevents fibrillization and diminishes vibrational modes associated to β sheet in tau protein linked to Alzheimer’s disease Cornejo, Alberto Aguilar Sandoval, Felipe Caballero, Leonardo Machuca, Luis Muñoz, Patricio Caballero, Julio Perry, George Ardiles, Alejandro Areche, Carlos Melo, Francisco J Enzyme Inhib Med Chem Research Paper Alzheimer’s disease is a common tauopathy where fibril formation and aggregates are the hallmark of the disease. Efforts targeting amyloid-β plaques have succeeded to remove plaques but failed in clinical trials to improve cognition; thus, the current therapeutic strategy is at preventing tau aggregation. Here, we demonstrated that four phenolic diterpenoids and rosmarinic acid inhibit fibrillization. Since, rosmarinic acid was the most active compound, we observe morphological changes in atomic force microscopy images after treatment. Hence, rosmarinic acid leads to a decrease in amide regions I and III, indicating that rosmarinic acid prevents β-sheet assembly. Molecular docking study inside the steric zipper model of the hexapeptide (306)VQIVYK(311) involved in fibrillization and β sheet formation, suggests that rosmarinic acid binds to the steric zipper with similar chemical interactions with respect to those observed for orange G, a known pharmacofore for amyloid. Taylor & Francis 2017-07-13 /pmc/articles/PMC6009890/ /pubmed/28701064 http://dx.doi.org/10.1080/14756366.2017.1347783 Text en © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Cornejo, Alberto Aguilar Sandoval, Felipe Caballero, Leonardo Machuca, Luis Muñoz, Patricio Caballero, Julio Perry, George Ardiles, Alejandro Areche, Carlos Melo, Francisco Rosmarinic acid prevents fibrillization and diminishes vibrational modes associated to β sheet in tau protein linked to Alzheimer’s disease |
title | Rosmarinic acid prevents fibrillization and diminishes vibrational modes associated to β sheet in tau protein linked to Alzheimer’s disease |
title_full | Rosmarinic acid prevents fibrillization and diminishes vibrational modes associated to β sheet in tau protein linked to Alzheimer’s disease |
title_fullStr | Rosmarinic acid prevents fibrillization and diminishes vibrational modes associated to β sheet in tau protein linked to Alzheimer’s disease |
title_full_unstemmed | Rosmarinic acid prevents fibrillization and diminishes vibrational modes associated to β sheet in tau protein linked to Alzheimer’s disease |
title_short | Rosmarinic acid prevents fibrillization and diminishes vibrational modes associated to β sheet in tau protein linked to Alzheimer’s disease |
title_sort | rosmarinic acid prevents fibrillization and diminishes vibrational modes associated to β sheet in tau protein linked to alzheimer’s disease |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009890/ https://www.ncbi.nlm.nih.gov/pubmed/28701064 http://dx.doi.org/10.1080/14756366.2017.1347783 |
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