The flavonoid luteolin reduces amyloid-β peptide (Aβ) generation. Luteolin is also a selective GSK-3 inhibitor that 1) decreases amyloidogenic γ-secretase APP processing, and 2) promotes presenilin 1 (PS1) carboxyl-terminal fragment (CTF) phosphorylation. GSK-3α activity is essential for both PS1 CTF phosphorylation states and PS1-APP interaction. These findings were validated in vivo, using a Tg2576 Alzheimers Disease model system. Luteolin treatment decreased soluble Aβ levels, reduced GSK-3 activity, and disrupted PS1-APP association. In addition, Tg2576 mice treated with diosmin, a glycoside of a flavone structurally and functionally similar to luteolin (diosmetin), displayed significantly reduced Aβ pathology as well.
