University of South Florida

Doug Shytle

Jun Tan

Kavon Rezai-Zadeh

The flavonoid luteolin reduces amyloid-&#x3b2; peptide (A&#x3b2;) generation. Luteolin is also a selective GSK-3 inhibitor that 1) decreases amyloidogenic &#x3b3;-secretase APP processing, and 2) promotes presenilin 1 (PS1) carboxyl-terminal fragment (CTF) phosphorylation. GSK-3&#x3b1; activity is essential for both PS1 CTF phosphorylation states and PS1-APP interaction. These findings were validated in vivo, using a Tg2576 Alzheimer's Disease model system. Luteolin treatment decreased soluble A&#x3b2; 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 A&#x3b2; pathology as well.

Flavonoid treatment of glycogen synthase kinase-based disease

The bioflavonoid luteolin reduces amyloid-&#x3b2; peptide (A&#x3b2;) generation. Luteolin is also a selective GSK-3 inhibitor that 1) decreases amyloidogenic &#x3b3;-secretase APP processing, and 2) promotes presenilin-1 (PS1) carboxyl-terminal fragment (CTF) phosphorylation. GSK-3&#x3b1; activity is essential for both PS1 CTF phosphorylation states and PS1-APP interaction. To validate The findings were validated in vivo, using a Tg2576 Alzheimer's Disease model system. Luteolin treatment decreased soluble A&#x3b2; levels, reduced GSK-3 activity, and disrupted PS1-APP association.

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Lutz, FL, United States of America

Doug Shytle