Nobiletin, a citrus flavonoid, improves memory impairment and Abeta pathology in a transgenic mouse model of Alzheimer's disease
| Autor: | Yasushi Ohizumi, Daisuke Saigusa, Tohru Yamakuni, Naomi Tetsu, Ryong Woon Shin, Hiroshi Onozuka, Koichi Ogino, Akihito Yokosuka, Yoshihiro Mimaki, Kentaro Matsuzaki, Yutaka Sashida, Akira Nakajima |
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| Rok vydání: | 2008 |
| Předmět: |
Genetically modified mouse
Pathology medicine.medical_specialty Citrus Transgene Hippocampus Mice Transgenic Nobiletin chemistry.chemical_compound Mice Alzheimer Disease mental disorders Amyloid precursor protein Medicine Animals Protein kinase A Pharmacology Flavonoids Memory Disorders Amyloid beta-Peptides biology business.industry Kinase medicine.disease Flavones Mice Inbred C57BL Disease Models Animal chemistry biology.protein Molecular Medicine Alzheimer's disease business |
| Zdroj: | The Journal of pharmacology and experimental therapeutics. 326(3) |
| ISSN: | 1521-0103 |
| Popis: | Increasing evidence suggests that the elevation of beta-amyloid (Abeta) 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 Abeta-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 Abeta(1-40) and Abeta(1-42) in the brain. Furthermore, consistent with the results of ELISA, by immunohistochemistry with anti-Abeta antibody, it was evidently shown that the administration of nobiletin decreased the Abeta 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. |
| Databáze: | OpenAIRE |
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