AβPP-selective BACE inhibitors (ASBI): novel class of therapeutic agents for alzheimer's disease.
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.
Buck Institute for Research on Aging, Novato, CA, USA.
Olivier
O
Descamps
Patricia
P
Spilman
Qiang
Q
Zhang
Clare P
CP
Libeu
Karen
K
Poksay
Olivia
O
Gorostiza
Jesus
J
Campagna
Barbara
B
Jagodzinska
Dale E
DE
Bredesen
Varghese
V
John
D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002461:Cell Line, Transformed; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D020890:Neuregulin-1 / Q000378:metabolism; D011485:Protein Binding; D012431:Rutin / Q000737:chemistry / Q000494:pharmacology; D020349:Surface Plasmon Resonance; D013997:Time Factors; D014162:Transfection
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D005419:Flavonoids; D020890:Neuregulin-1; C037032:galangin; D012431:Rutin; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases