| First Author | Cox CJ | Year | 2015 |
| Journal | Neurobiol Aging | Volume | 36 |
| Issue | 1 | Pages | 178-87 |
| PubMed ID | 25316600 | Mgi Jnum | J:218405 |
| Mgi Id | MGI:5617429 | Doi | 10.1016/j.neurobiolaging.2014.07.032 |
| Citation | Cox CJ, et al. (2015) Dietary (-)-epicatechin as a potent inhibitor of betagamma-secretase amyloid precursor protein processing. Neurobiol Aging 36(1):178-87 |
| abstractText | Flavonoids, a group of dietary polyphenols have been shown to possess cognitive health benefits. Epidemiologic evidence suggests that they could play a role in risk reduction in dementia. Amyloid precursor protein processing and the subsequent generation of amyloid beta (Abeta) are central to the pathogenesis of Alzheimer's disease, as soluble, oligomeric Abeta is thought to be the toxic species driving disease progression. We undertook an in vitro screen to identify flavonoids with bioactivity at betagamma-mediated amyloid precursor protein processing, which lead to identification of a number of flavonoids bioactive at 100 nM. Because of known bioavailability, we investigated the catechin family further and identified epigallocatechin and (-)-epicatechin as potent (nanomolar) inhibitors of amyloidogenic processing. Supporting this finding, we have shown reduced Abeta pathology and Abeta levels following short term, a 21-day oral delivery of (-)-epicatechin in 7-month-old TASTPM mice. Further, in vitro mechanistic studies suggest this is likely because of indirect BACE1 inhibition. Taken together, our results suggest that orally delivered (-)-epicatechin may be a potential prophylactic for Alzheimer's disease. |
