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

Autor: Alberto Cornejo, Felipe Aguilar Sandoval, Leonardo Caballero, Luis Machuca, Patricio Muñoz, Julio Caballero, George Perry, Alejandro Ardiles, Carlos Areche, Francisco Melo
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 32, Iss 1, Pp 945-953 (2017)
Druh dokumentu: article
ISSN: 1475-6366
1475-6374
14756366
DOI: 10.1080/14756366.2017.1347783
Popis: 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.
Databáze: Directory of Open Access Journals
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