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Article type: Research Article
Authors: Descamps, Oliviera | Spilman, Patriciaa | Zhang, Qianga | Libeu, Clare P.a | Poksay, Karena | Gorostiza, Oliviaa | Campagna, Jesusa | Jagodzinska, Barbaraa; c | Bredesen, Dale E.a; b; *; 1 | John, Varghesea; c; *; 1
Affiliations: [a] Buck Institute for Research on Aging, Novato, CA, USA | [b] Department of Neurology, University of California, San Francisco, CA, USA | [c] Dominican University of California, San Rafael, CA, USA
Correspondence: [*] Correspondence to: Varghese John or Dale E. Bredesen, Buck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USA. Tel.: +1 415 4093 3651; Fax: +1 415 209 2230; E-mail: [email protected].
Note: [1] These two authors share senior authorship.
Abstract: A systematic approach was used to identify AβPP-selective BACE inhibitors (ASBI) and to evaluate their in vivo ability to modulate AβPP processing selectively. We identified a bioflavonoid nutritional supplement as a molecular lead that acts as an ASBI in cell models, and show that increasing brain levels of this bioflavonoid through a pro-drug approach leads to reduction of Aβ42 in an Alzheimer's disease mouse model. ASBIs represent a novel class of candidate therapeutic agents for Alzheimer's disease.
Keywords: Alzheimer's disease, AβPP, ASBI, galangin, pro-drug, rutin
DOI: 10.3233/JAD-130578
Journal: Journal of Alzheimer's Disease, vol. 37, no. 2, pp. 343-355, 2013
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