RT Journal Article
SR Electronic
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
FD American Society for Pharmacology and Experimental Therapeutics
SP 739
OP 744
DO 10.1124/jpet.108.140293
VO 326
IS 3
A1 Hiroshi Onozuka
A1 Akira Nakajima
A1 Kentaro Matsuzaki
A1 Ryong-Woon Shin
A1 Koichi Ogino
A1 Daisuke Saigusa
A1 Naomi Tetsu
A1 Akihito Yokosuka
A1 Yutaka Sashida
A1 Yoshihiro Mimaki
A1 Tohru Yamakuni
A1 Yasushi Ohizumi
YR 2008
UL http://jpet.aspetjournals.org/content/326/3/739.abstract
AB 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