期刊
NEUROSCIENCE LETTERS
卷 400, 期 3, 页码 230-234出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2006.02.077
关键词
nobiletin; Alzheimer's disease model rats; memory; PKA/CREB-dependent signaling pathway
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive and memory deterioration. Production and accumulation of P-amyloid peptide (AP) is central to the pathogenesis of AD. Recent studies have demonstrated that PKA/CREB-dependent signaling pathway and long-term potentiation are inhibited by sublethal concentrations of A beta(1-42) in cultured hippocampus neurons. Here, we examined the effects of nobiletin on the A beta-induced inhibition of CREB phosphorylation in cultured rat hippocampus neurons. A sublethal concentration of A beta(1-42) or A beta(1-40) decreased glutamate-induced CREB phosphorylation, whereas pretreatment with nobiletin reversed the A beta-induced decrease in CREB phosphorylation. The effects of nobiletin on impairment of learning ability were also examined in chronically A beta(1-40) infused AD model rats using the eight-arm radial maze. In the AD model rats, nobiletin showed protective effects on A beta(1-40)-induced impairment of learning ability. These results suggest that nobiletin has the potential for becoming a novel lead compound for drug development for AD. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
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