Dietary (−)-epicatechin as a potent inhibitor of βγ-secretase amyloid precursor protein processing☆
| Autor: | Cox, Carla J., Choudhry, Fahd, Peacey, Eleanor, Perkinton, Michael S., Richardson, Jill C., Howlett, David R., Lichtenthaler, Stefan F., Francis, Paul T., Williams, Robert J. |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
APP processing Neuroscience(all) Clinical Neurology metabolism [Amyloid beta-Peptides] administration & dosage [Catechin] Administration Oral genetics [Alzheimer Disease] Mice Transgenic prevention & control [Alzheimer Disease] Catechin Pharmacology Toxicology and Pharmaceutics(all) Amyloid beta-Protein Precursor gallocatechol Alzheimer Disease metabolism [Amyloid beta-Protein Precursor] Animals ddc:610 Amyloid pathology Cells Cultured Aβ Amyloid beta-Peptides Biochemistry Genetics and Molecular Biology(all) analogs & derivatives [Catechin] Brain Regular Article BACE1 Alzheimer's disease Ageing metabolism [Brain] Flavonoid Dietary polyphenolic Disease Progression pharmacology [Catechin] Flavanol Dementia Geriatrics and Gerontology TASTPM Developmental Biology |
| Zdroj: | Neurobiology of Aging Cox, C J, Choudhry, F, Peacey, E, Perkinton, M S, Richardson, J C, Howlett, D R, Lichtenthaler, S F, Francis, P T & Williams, R J 2015, ' Dietary (-)-epicatechin as a potent inhibitor of βγ-secretase amyloid precursor protein processing ', Neurobiology of Aging, vol. 36, no. 1, pp. 178-187 . https://doi.org/10.1016/j.neurobiolaging.2014.07.032 Neurobiology of aging 36(1), 178-187 (2015). doi:10.1016/j.neurobiolaging.2014.07.032 |
| ISSN: | 1558-1497 0197-4580 |
| DOI: | 10.1016/j.neurobiolaging.2014.07.032 |
| Popis: | 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 (Aβ) are central to the pathogenesis of Alzheimer's disease, as soluble, oligomeric Aβ is thought to be the toxic species driving disease progression. We undertook an in vitro screen to identify flavonoids with bioactivity at βγ-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 Aβ pathology and Aβ 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. |
| Databáze: | OpenAIRE |
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