Abstract
This chapter further demonstrates the scope and scale of the pleiotropic capabilities of the curcuminoids, resveratrol, and (-)-epigallocatechin-3-gallate (EGCG) formula by reporting that it safely inhibits Notch-1 signaling, inhibits glycogen synthase kinase 3 beta, blocks activation of mitogen-activated protein kinases, inhibits microglial activation, reduces N-methyl-d-aspartate–mediated excitotoxic neuronal cell death, inhibits nuclear factor kappa B activation, reduces interleukin-1beta, interleukin-6, and tumor necrosis factor alpha, and chelates iron and copper from the brain. The extensive multitargeting of these compounds point toward a “pleiotropic theory” of plant polyphenols, pursuant to (1) the multitargeting abilities of the polyphenols that conform to the multidimensional pathophysiology of Alzheimer's disease (AD), (2) the aligned results of the mechanistic, epidemiological, and population studies of the polyphenolic compounds and their parent ancient foods, (3) the global pleiotropism of the plant polyphenols, which encompass both amyloid- and tau-based pathologies and other pathogenic models of AD, and (4) the trans-stage ability to therapeutically address the pathophysiological demands of the zero, preclinical, prodromal, and clinical dementia stages of AD.
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