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題 名 | Molecular Pathogenesis, Treatment Strategies and Animal Models of Alzheimer's Disease |
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作 者 | 蕭永基; 王春女; | 書刊名 | 中華藥學雜誌 |
卷 期 | 54:1 民91.02 |
頁 次 | 頁1-16 |
分類號 | 415.149 |
關鍵詞 | 阿茲海默氏症; Alzheimer's disease; Amyloid β; Neurotoxicity; Animal model; |
語 文 | 英文(English) |
英文摘要 | Senile plaques and neurofilament tangles are the hall marks of Alzheimers disease (AD). Amyloid b protein (Ab), the major protein component of se nile plaques, has been suggested to play an important role in the pathogenesis of AD. Ab is proteolytically derived from amyloid precursor protein, which is widely ex pressed through out the brain. Multiple lines of evidence have demonstrated that fibril Ab participates in the induction of neuronal death and neuritic changes. The neurotoxic effects of A b may be mediated by perturbation of calcium homeosta sis and production of reactive oxygen species (ROS). Several agents are neuroprotective in vitro by targeting specific pathways responsible for Ab-induced toxicity. These agents include antioxidants, freeradical scavengers and caspase inhibitors. Flavonoids, the so-called phytoestrogens, display both antioxidative and antiproliferative activities. We have demonstrated that the neuronal apoptosis induced by Ab is inhibited by kaempferol, and to a lesser extent by apigenin. Kaempferol exhibits antioxidative activity and decreases the ROS accumulation in duced by Ab, whereas apigenin only shows a marginal effect on ROS levels. These results indicate that blockade of the caspase cascade is responsible for the neuroprotective effects of phytoestrogens on Ab-mediated neurotoxicity. Inhibition of the caspase cascade in com bination with antioxidative activity may further reduce Ab-mediated neurotoxicity. Some animal models have been used to study AD. A transgenic mouse, Tg2576, has been established by over-expressing the mutated human Ab precursor protein. The correlative appearance of behavioral, biochemical, and pathological abnormalities reminiscent of Alzheimer's disease in these transgenic mice suggests new opportunities for exploring the pathophysiology and neurobiology of this disease. |
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