Interaction of cinnamaldehyde and epicatechin with tau: implications of beneficial effects in modulating Alzheimer's disease pathogenesis
- PMID: 23531502
- DOI: 10.3233/JAD-122113
Interaction of cinnamaldehyde and epicatechin with tau: implications of beneficial effects in modulating Alzheimer's disease pathogenesis
Abstract
Abnormal modifications in tau such as hyperphosphorylation, oxidation, and glycation interfere with its interaction with microtubules leading to its dissociation and self-aggregation into neurofibrillary tangles, a hallmark of Alzheimer's disease (AD). Previously we reported that an aqueous extract of cinnamon has the ability to inhibit tau aggregation in vitro and can even induce dissociation of tangles isolated from AD brain. In the present study, we carried out investigations with cinnamaldehyde (CA) and epicatechin (EC), two components of active cinnamon extract. We found that CA and the oxidized form of EC (ECox) inhibited tau aggregation in vitro and the activity was due to their interaction with the two cysteine residues in tau. Mass spectrometry of a synthetic peptide, SKCGS, representing the actual tau sequence, identified the thiol as reacting with CA and ECox. Use of a cysteine double mutant of tau showed the necessity of cysteine for aggregation inhibition by CA. The interaction of CA with tau cysteines was reversible and the presence of CA did not impair the biological function of tau in tubulin assembly in vitro. Further, these compounds protected tau from oxidation caused by the reactive oxygen species, H2O2, and prevented subsequent formation of high molecular weight species that are considered to stimulate tangle formation. Finally, we observed that EC can sequester highly reactive and toxic byproducts of oxidation such as acrolein. Our results suggest that small molecules that form a reversible interaction with cysteines have the potential to protect tau from abnormal modifications.
Similar articles
-
Cinnamon extract inhibits tau aggregation associated with Alzheimer's disease in vitro.J Alzheimers Dis. 2009;17(3):585-97. doi: 10.3233/JAD-2009-1083. J Alzheimers Dis. 2009. PMID: 19433898
-
Modification of tau to an Alzheimer's type protein interferes with its interaction with microtubules.Cell Mol Biol (Noisy-le-grand). 1998 Nov;44(7):1117-27. Cell Mol Biol (Noisy-le-grand). 1998. PMID: 9846894
-
Molecules of the quinoline family block tau self-aggregation: implications toward a therapeutic approach for Alzheimer's disease.J Alzheimers Dis. 2012;29(1):79-88. doi: 10.3233/JAD-2011-110995. J Alzheimers Dis. 2012. PMID: 22232002
-
Probable participation of 14-3-3 in tau protein oligomerization and aggregation.J Alzheimers Dis. 2011;27(3):467-76. doi: 10.3233/JAD-2011-110692. J Alzheimers Dis. 2011. PMID: 21876254 Review.
-
Tau oligomers and aggregation in Alzheimer's disease.J Neurochem. 2010 Mar;112(6):1353-67. doi: 10.1111/j.1471-4159.2009.06511.x. Epub 2009 Nov 27. J Neurochem. 2010. PMID: 19943854 Review.
Cited by 19 articles
-
Wenyang Jieyu Decoction Alleviates Depressive Behavior in the Rat Model of Depression via Regulation of the Intestinal Microbiota.Evid Based Complement Alternat Med. 2020 Jul 23;2020:3290450. doi: 10.1155/2020/3290450. eCollection 2020. Evid Based Complement Alternat Med. 2020. PMID: 32774410 Free PMC article.
-
The methanolic extract of Cinnamomum zeylanicum bark improves formaldehyde-induced neurotoxicity through reduction of phospho-tau (Thr231), inflammation, and apoptosis.EXCLI J. 2020 May 25;19:671-686. eCollection 2020. EXCLI J. 2020. PMID: 32536837 Free PMC article.
-
Advances in protein misfolding, amyloidosis and its correlation with human diseases.3 Biotech. 2020 May;10(5):193. doi: 10.1007/s13205-020-2166-x. Epub 2020 Apr 4. 3 Biotech. 2020. PMID: 32269898 Review.
-
Coniferaldehyde attenuates Alzheimer's pathology via activation of Nrf2 and its targets.Theranostics. 2020 Jan 1;10(1):179-200. doi: 10.7150/thno.36722. eCollection 2020. Theranostics. 2020. PMID: 31903114 Free PMC article.
-
Nature's Derivative(s) as Alternative Anti-Alzheimer's Disease Treatments.J Alzheimers Dis Rep. 2019 Nov 21;3(1):279-297. doi: 10.3233/ADR-190137. J Alzheimers Dis Rep. 2019. PMID: 31867567 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grant support
LinkOut - more resources
-
Full Text Sources
-
Other Literature Sources
-
Medical
-
Research Materials