Neuroprotective Effects of Natural Products: Interaction with Intracellular Kinases, Amyloid Peptides and a Possible Role for Transthyretin
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Various studies reported on the neuroprotective effects of natural products, particularly polyphenols, widely present in food and beverages. For example, we have shown that resveratrol, a polyphenol contained present in red wine and other foods, activates the phosphorylation of protein kinase C (PKC), this effect being involved in its neuroprotective action against Aß-induced toxicity. Moreover, tea-derived catechin gallate esters inhibit the formation Aß oligomers/fibrils, suggesting that this action likely contributes to their neuroprotective effects. Interestingly, the effects of polyphenols may be attributable, at least in part, to the presence of specific binding sites. Autoradiographic studies revealed that these binding sites are particularly enriched in choroids plexus in the rat brain. Interestingly, the choroid plexus secretes transthyretin, a protein that has been shown to prevent Aβ aggregation and that may be critical to the maintenance of normal learning capacities in aging. Taken together, these data suggest that polyphenols target multiple enzymes/proteins leading to their neuroprotective actions.
KeywordsAlzheimer’s disease Aß peptides Resveratrol Tea catechins Transthyretin Polyphenols Neuroprotection Beta-amyloid PKC
This work was supported by grants from the Canadian Institutes of Health Research (CIHR) to R.Q. and a student scholarship from CIHR to J.B.
- 8.Bastianetto S, Quirion R (2001) Resveratrol and red wine constituents: evaluation of their neuroprotective properties. Pharmacol News 8:33–38Google Scholar
- 20.Rezai-Zadeh K, Shytle D, Sun N, Mori T, Hou H, Jeanniton D, Ehrhart J, Townsend K, Zeng J, Morgan D, Hardy J, Town T, Tan J (2005) Green tea epigallocatechin-3-gallate (EGCG) modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice. J Neurosci 25:8807–8814PubMedCrossRefGoogle Scholar
- 21.Riviere C, Richard T, Quentin L, Krisa S, Merillon JM, Monti JP (2006) Inhibitory activity of stilbenes on Alzheimer’s beta-amyloid fibrils in vitro. Bioorg Med Chem [Epub ahead of print]Google Scholar
- 28.Stein TD, Anders NJ, DeCarli C, Chan SL, Mattson MP, Johnson JA (2004) Neutralization of transthyretin reverses the neuroprotective effects of secreted amyloid precursor protein (APP) in APPSW mice resulting in tau phosphorylation and loss of hippocampal neurons: support for the amyloid hypothesis. J Neurosci 24:7707–7717PubMedCrossRefGoogle Scholar
- 36.Zanassi P, Paolillo M, Feliciello A, Avvedimento EV, Gallo V, Schinelli S (2001) cAMP-dependent protein kinase induces cAMP-response element-binding protein phosphorylation via an intracellular calcium release/ERK-dependent pathway in striatal neurons. J Biol Chem 276:11487–11495PubMedCrossRefGoogle Scholar
- 43.Tsuzuki K, Fukatsu R, Yamaguchi H, Tateno M, Imai K, Fujii N, Yamauchi T (2000) Transthyretin binds amyloid beta peptides, Abeta1–42 and Abeta1–40 to form complex in the autopsied human kidney—possible role of transthyretin for abeta sequestration. Neurosci Lett 281:171–174PubMedCrossRefGoogle Scholar