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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amyloid Precursor Protein Secretases / antagonists & inhibitors*
-
Amyloid Precursor Protein Secretases / metabolism*
-
Amyloid beta-Peptides / metabolism
-
Amyloid beta-Protein Precursor / genetics
-
Amyloid beta-Protein Precursor / metabolism*
-
Animals
-
Aspartic Acid Endopeptidases
-
Brain / drug effects
-
Brain / metabolism
-
Cell Line, Transformed
-
Cricetulus
-
Dose-Response Relationship, Drug
-
Flavonoids / chemistry
-
Flavonoids / pharmacokinetics
-
Flavonoids / pharmacology*
-
Humans
-
Mice
-
Neuregulin-1 / metabolism
-
Protein Binding
-
Rutin / chemistry
-
Rutin / pharmacology
-
Surface Plasmon Resonance
-
Time Factors
-
Transfection
Substances
-
Amyloid beta-Peptides
-
Amyloid beta-Protein Precursor
-
Flavonoids
-
Neuregulin-1
-
galangin
-
Rutin
-
Amyloid Precursor Protein Secretases
-
Aspartic Acid Endopeptidases