Rosmarinic acid prevents fibrillization and diminishes vibrational modes associated to β sheet in tau protein linked to Alzheimer’s disease

Alberto Cornejo, Felipe Aguilar Sandoval, Leonardo Caballero, Luis Machuca, Patricio Muñoz, Julio Caballero, George Perry, Alejandro Ardiles, Carlos Areche, Francisco Melo

Resultado de la investigación: Article

12 Citas (Scopus)

Resumen

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 306VQIVYK311 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.

Idioma originalEnglish
Páginas (desde-hasta)945-953
Número de páginas9
PublicaciónJournal of Enzyme Inhibition and Medicinal Chemistry
Volumen32
N.º1
DOI
EstadoPublished - 1 ene 2017

Huella dactilar

tau Proteins
Alzheimer Disease
Tauopathies
Diterpenes
Atomic Force Microscopy
Amyloid Plaques
Amyloid
Amides
Cognition
rosmarinic acid
Clinical Trials

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Medicine(all)

Citar esto

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. En: Journal of Enzyme Inhibition and Medicinal Chemistry. 2017 ; Vol. 32, N.º 1. pp. 945-953.
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abstract = "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 306VQIVYK311 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.",
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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.

En: Journal of Enzyme Inhibition and Medicinal Chemistry, Vol. 32, N.º 1, 01.01.2017, p. 945-953.

Resultado de la investigación: Article

TY - JOUR

T1 - Rosmarinic acid prevents fibrillization and diminishes vibrational modes associated to β sheet in tau protein linked to Alzheimer’s disease

AU - Cornejo, Alberto

AU - Aguilar Sandoval, Felipe

AU - Caballero, Leonardo

AU - Machuca, Luis

AU - Muñoz, Patricio

AU - Caballero, Julio

AU - Perry, George

AU - Ardiles, Alejandro

AU - Areche, Carlos

AU - Melo, Francisco

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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 306VQIVYK311 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.

AB - 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 306VQIVYK311 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.

KW - aggregation

KW - Alzheimer’s disease

KW - inhibition

KW - pharmacophore

KW - tau

KW - β-sheet

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