Inhibition of tau fibrillization by oleocanthal via reaction with the amino groups of tau. Export

@article{citeulike:5973369, abstract = {Tau is a microtubule-associated protein that promotes microtubule assembly and stability. In Alzheimer's disease and related tauopathies, tau fibrillizes and aggregates into neurofibrillary tangles. Recently, oleocanthal isolated from extra virgin olive oil was found to display non-steroidal anti-inflammatory activity similar to ibuprofen. As our unpublished data indicates an inhibitory effect of oleocanthal on amyloid beta peptide fibrillization, we reasoned that it might inhibit tau fibrillization as well. Herein, we demonstrate that oleocanthal abrogates fibrillization of tau by locking tau into the naturally unfolded state. Using PHF6 consisting of the amino acid residues VQIVYK, a hexapeptide within the third repeat of tau that is essential for fibrillization, we show that oleocanthal forms an adduct with the lysine via initial Schiff base formation. Structure and function studies demonstrate that the two aldehyde groups of oleocanthal are required for the inhibitory activity. These two aldehyde groups show certain specificity when titrated with free lysine and oleocanthal does not significantly affect the normal function of tau. These findings provide a potential scheme for the development of novel therapies for neurodegenerative tauopathies.}, author = {Li, Wenkai and Sperry, Jeffrey B. and Crowe, Alex and Trojanowski, John Q. and Smith, Amos B. and Lee, Virginia M-Y M.}, citeulike-article-id = {5973369}, citeulike-linkout-0 = {http://dx.doi.org/10.1111/j.1471-4159.2009.06224.x}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19549281}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19549281}, doi = {10.1111/j.1471-4159.2009.06224.x}, issn = {1471-4159}, journal = {Journal of neurochemistry}, keywords = {oleocanthal, tau}, month = {August}, number = {4}, pages = {1339--1351}, posted-at = {2009-10-20 09:40:46}, priority = {2}, title = {Inhibition of tau fibrillization by oleocanthal via reaction with the amino groups of tau.}, url = {http://dx.doi.org/10.1111/j.1471-4159.2009.06224.x}, volume = {110}, year = {2009} }

TY - JOUR ID - citeulike:5973369 L3 - citeulike-article-id:5973369 N2 - Tau is a microtubule-associated protein that promotes microtubule assembly and stability. In Alzheimer's disease and related tauopathies, tau fibrillizes and aggregates into neurofibrillary tangles. Recently, oleocanthal isolated from extra virgin olive oil was found to display non-steroidal anti-inflammatory activity similar to ibuprofen. As our unpublished data indicates an inhibitory effect of oleocanthal on amyloid beta peptide fibrillization, we reasoned that it might inhibit tau fibrillization as well. Herein, we demonstrate that oleocanthal abrogates fibrillization of tau by locking tau into the naturally unfolded state. Using PHF6 consisting of the amino acid residues VQIVYK, a hexapeptide within the third repeat of tau that is essential for fibrillization, we show that oleocanthal forms an adduct with the lysine via initial Schiff base formation. Structure and function studies demonstrate that the two aldehyde groups of oleocanthal are required for the inhibitory activity. These two aldehyde groups show certain specificity when titrated with free lysine and oleocanthal does not significantly affect the normal function of tau. These findings provide a potential scheme for the development of novel therapies for neurodegenerative tauopathies. IS - 4 JF - Journal of neurochemistry SN - 1471-4159 EP - 1351 TI - Inhibition of tau fibrillization by oleocanthal via reaction with the amino groups of tau. VL - 110 SP - 1339 KW - oleocanthal KW - tau AU - Li, Wenkai AU - Sperry, Jeffrey AU - Crowe, Alex AU - Trojanowski, John AU - Smith, Amos AU - Lee, Virginia M-Y PY - 2009/08// UR - http://dx.doi.org/10.1111/j.1471-4159.2009.06224.x ER -