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

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.

Keywords:

• Alzheimer’s disease
• tau
• aggregation
• β-sheet
• inhibition
• pharmacophore

Acknowledgements

This work was supported from INACH RT 13–13 and Fondecyt Regular No 1150745 to Alberto Cornejo and Carlos Areche. Francisco Melo, Felipe Aguilar and Leonardo Caballero kindly acknowledge Anillo ACT1412 Conicyt-Chile. George Perry acknowledges The Semmes Foundation and a grant from the National Institute on Minority Health and Health Disparities (G12MD00759) from the National Institutes of Health.

Disclosure statement

Authors declare no conflict of interest.

Additional information

Funding

This work was supported from INACH RT 13–13 and Fondecyt Regular No 1150745 to Alberto Cornejo and Carlos Areche. Francisco Melo, Felipe Aguilar and Leonardo Caballero kindly acknowledge Anillo ACT1412 Conicyt-Chile. George Perry acknowledges The Semmes Foundation and a grant from the National Institute on Minority Health and Health Disparities (G12MD00759) from the National Institutes of Health.