TY - JOUR T1 - Nobiletin, a Citrus Flavonoid, Improves Memory Impairment and Aβ Pathology in a Transgenic Mouse Model of Alzheimer's Disease JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 739 LP - 744 DO - 10.1124/jpet.108.140293 VL - 326 IS - 3 AU - Hiroshi Onozuka AU - Akira Nakajima AU - Kentaro Matsuzaki AU - Ryong-Woon Shin AU - Koichi Ogino AU - Daisuke Saigusa AU - Naomi Tetsu AU - Akihito Yokosuka AU - Yutaka Sashida AU - Yoshihiro Mimaki AU - Tohru Yamakuni AU - Yasushi Ohizumi Y1 - 2008/09/01 UR - http://jpet.aspetjournals.org/content/326/3/739.abstract N2 - Increasing evidence suggests that the elevation of β-amyloid (Aβ) peptides in the brain is central to the pathogenesis of Alzheimer's disease (AD). Our recent studies have demonstrated that nobiletin, a polymethoxylated flavone from citrus peels, enhances cAMP/protein kinase A/extracellular signal-regulated kinase/cAMP response element-binding protein signaling in cultured hippocampal neurons and ameliorates Aβ-induced memory impairment in AD model rats. For the first time, we report that this natural compound improves memory deficits in amyloid precursor protein (APP) transgenic mice that overexpress human APP695 harboring the double Swedish and London mutations [APP-SL 7-5 transgenic (Tg) mice]. Our enzyme-linked immunosorbent assay (ELISA) also showed that administration of nobiletin to the transgenic mice for 4 months markedly reduced quantity of guanidine-soluble Aβ1–40 and Aβ1–42 in the brain. Furthermore, consistent with the results of ELISA, by immunohistochemistry with anti-Aβ antibody, it was evidently shown that the administration of nobiletin decreased the Aβ burden and plaques in the hippocampus of APP-SL 7-5 Tg mice. These findings suggest that this natural compound has potential to become a novel drug for fundamental treatment of AD. The American Society for Pharmacology and Experimental Therapeutics ER -