2017 |
Cornejo, A; Sandoval, F A; Caballero, L; Machuca, L; Munoz, P; Caballero, J; Perry, G; Ardiles, A; Areche, C; Melo, F Rosmarinic Acid Prevents Fibrillization and Diminishes Vibrational Modes Associated to Beta Sheet in Tau Protein Linked to Alzheimer's Disease Artículo de revista Journal of Enzyme Inhibition and Medicinal Chemistry, 32 (1), pp. 945-953, 2017, ISSN: 1475-6366. Resumen | Enlaces | BibTeX | Etiquetas: alzheimer's amyloid beta-sheet, carnosic cells criteria, disease, fibril filaments, formation, helical in-vitro, inhibition, inhibitors, mice, neuropathologic paired pharmacophore, salvia-officinalis, tau transgenic @article{RN337, title = {Rosmarinic Acid Prevents Fibrillization and Diminishes Vibrational Modes Associated to Beta Sheet in Tau Protein Linked to Alzheimer's Disease}, author = { A. Cornejo and F.A. Sandoval and L. Caballero and L. Machuca and P. Munoz and J. Caballero and G. Perry and A. Ardiles and C. Areche and F. Melo}, url = {/brokenurl#<Go to ISI>://WOS:000406130000006}, doi = {10.1080/14756366.2017.1347783}, issn = {1475-6366}, year = {2017}, date = {2017-01-01}, journal = {Journal of Enzyme Inhibition and Medicinal Chemistry}, volume = {32}, number = {1}, pages = {945-953}, abstract = {Alzheimer's disease is a common tauopathy where fibril formation and aggregates are the hallmark of the disease. Efforts targeting amyloid-beta 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 beta-sheet assembly. Molecular docking study inside the steric zipper model of the hexapeptide (306)VQIVYK(311) involved in fibrillization and beta 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 amyloid beta-sheet, carnosic cells criteria, disease, fibril filaments, formation, helical in-vitro, inhibition, inhibitors, mice, neuropathologic paired pharmacophore, salvia-officinalis, tau transgenic}, pubstate = {published}, tppubtype = {article} } Alzheimer's disease is a common tauopathy where fibril formation and aggregates are the hallmark of the disease. Efforts targeting amyloid-beta 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 beta-sheet assembly. Molecular docking study inside the steric zipper model of the hexapeptide (306)VQIVYK(311) involved in fibrillization and beta 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. |
Chua, S W; Cornejo, A; Eersel, Van J; Stevens, C H; Vaca, I; Cueto, M; Kassiou, M; Gladbach, A; Macmillan, A; Lewis, L; Whan, R; Ittner, L M The Polyphenol Altenusin Inhibits in Vitro Fibrillization of Tau and Reduces Induced Tau Pathology in Primary Neurons Artículo de revista Acs Chemical Neuroscience, 8 (4), pp. 743-751, 2017, ISSN: 1948-7193. Resumen | Enlaces | BibTeX | Etiquetas: alzheimer's alzheimers-disease, antiaggregation, associated disease, filaments, helical methylene-blue, mice, microtubule model, mouse neurodegeneration, paired phosphorylation, protein tangles tau, tauopathy, transgenic @article{RN341, title = {The Polyphenol Altenusin Inhibits in Vitro Fibrillization of Tau and Reduces Induced Tau Pathology in Primary Neurons}, author = { S.W. Chua and A. Cornejo and J. Van Eersel and C.H. Stevens and I. Vaca and M. Cueto and M. Kassiou and A. Gladbach and A. Macmillan and L. Lewis and R. Whan and L.M. Ittner}, url = {/brokenurl#<Go to ISI>://WOS:000399968400009}, doi = {10.1021/acschemneuro.6b00433}, issn = {1948-7193}, year = {2017}, date = {2017-01-01}, journal = {Acs Chemical Neuroscience}, volume = {8}, number = {4}, pages = {743-751}, abstract = {In Alzheimer's disease, the microtubule-associated protein tau forms intracellular neurofibrillary tangles (NFTs). A critical step in the formation of NFTs is the conversion of soluble tau into insoluble filaments. Accordingly, a current therapeutic strategy in clinical trials is aimed at preventing tau aggregation. Here, we assessed altenusin, a bioactive polyphenolic compound, for its potential to inhibit tau aggregation. Altenusin inhibits aggregation of tau protein into paired helical filaments in vitro. This was associated with stabilization of, tau dimers and other oligomers into globular structures as revealed by atomic force microscopy. Moreover, altenusin reduced tau phosphorylation in cells expressing pathogenic tau, and prevented neuritic tau pathology induced by incubation of primary neurons with tau fibrils. However, treatment of tau transgenic mice did not improve neuropathology and functional deficits. Taken together, altenusin prevents tau fibrillization in vitro and induced tau pathology in neurons.}, keywords = {alzheimer's alzheimers-disease, antiaggregation, associated disease, filaments, helical methylene-blue, mice, microtubule model, mouse neurodegeneration, paired phosphorylation, protein tangles tau, tauopathy, transgenic}, pubstate = {published}, tppubtype = {article} } In Alzheimer's disease, the microtubule-associated protein tau forms intracellular neurofibrillary tangles (NFTs). A critical step in the formation of NFTs is the conversion of soluble tau into insoluble filaments. Accordingly, a current therapeutic strategy in clinical trials is aimed at preventing tau aggregation. Here, we assessed altenusin, a bioactive polyphenolic compound, for its potential to inhibit tau aggregation. Altenusin inhibits aggregation of tau protein into paired helical filaments in vitro. This was associated with stabilization of, tau dimers and other oligomers into globular structures as revealed by atomic force microscopy. Moreover, altenusin reduced tau phosphorylation in cells expressing pathogenic tau, and prevented neuritic tau pathology induced by incubation of primary neurons with tau fibrils. However, treatment of tau transgenic mice did not improve neuropathology and functional deficits. Taken together, altenusin prevents tau fibrillization in vitro and induced tau pathology in neurons. |
2017 |
Rosmarinic Acid Prevents Fibrillization and Diminishes Vibrational Modes Associated to Beta Sheet in Tau Protein Linked to Alzheimer's Disease Artículo de revista Journal of Enzyme Inhibition and Medicinal Chemistry, 32 (1), pp. 945-953, 2017, ISSN: 1475-6366. |
The Polyphenol Altenusin Inhibits in Vitro Fibrillization of Tau and Reduces Induced Tau Pathology in Primary Neurons Artículo de revista Acs Chemical Neuroscience, 8 (4), pp. 743-751, 2017, ISSN: 1948-7193. |