First Author | Mori T | Year | 2012 |
Journal | J Biol Chem | Volume | 287 |
Issue | 9 | Pages | 6912-27 |
PubMed ID | 22219198 | Mgi Jnum | J:182430 |
Mgi Id | MGI:5315633 | Doi | 10.1074/jbc.M111.294025 |
Citation | Mori T, et al. (2012) Tannic acid is a natural beta-secretase inhibitor that prevents cognitive impairment and mitigates Alzheimer-like pathology in transgenic mice. J Biol Chem 287(9):6912-27 |
abstractText | Amyloid precursor protein (APP) proteolysis is essential for production of amyloid-beta (Abeta) peptides that form beta-amyloid plaques in brains of Alzheimer disease (AD) patients. Recent focus has been directed toward a group of naturally occurring anti-amyloidogenic polyphenols known as flavonoids. We orally administered the flavonoid tannic acid (TA) to the transgenic PSAPP mouse model of cerebral amyloidosis (bearing mutant human APP and presenilin-1 transgenes) and evaluated cognitive function and AD-like pathology. Consumption of TA for 6 months prevented transgene-associated behavioral impairment including hyperactivity, decreased object recognition, and defective spatial reference memory, but did not alter nontransgenic mouse behavior. Accordingly, brain parenchymal and cerebral vascular beta-amyloid deposits and abundance of various Abeta species including oligomers were mitigated in TA-treated PSAPP mice. These effects occurred with decreased cleavage of the beta-carboxyl-terminal APP fragment, lowered soluble APP-beta production, reduced beta-site APP cleaving enzyme 1 protein stability and activity, and attenuated neuroinflammation. As in vitro validation, we treated well characterized mutant human APP-overexpressing murine neuron-like cells with TA and found significantly reduced Abeta production associated with less amyloidogenic APP proteolysis. Taken together, these results raise the possibility that dietary supplementation with TA may be prophylactic for AD by inhibiting beta-secretase activity and neuroinflammation and thereby mitigating AD pathology. |