How fisetin reduces the impact of age and disease on CNS function.
How fisetin reduces the impact of age and disease on CNS function.
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DOI：
10.2741/s425
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发表时间：
2015-06-01
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影响因子：
--
通讯作者：
Maher P
中科院分区：
文献类型：
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作者：
Maher P
越来越清楚的是，神经系统疾病是多因素的，涉及多个细胞系统的破坏。因此，虽然每种疾病都有自己的启动机制和病理，但某些共同的途径似乎与迄今为止所描述的大多数（如果不是全部）神经系统疾病有关。因此，仅调节单一因素不太可能有效地预防疾病发展或减缓疾病进展。一种更好的方法是识别具有与维持脑功能相关的多种生物活性的小分子（< 900道尔顿）。在过去的几年里，我们已经确定了一种口服活性的，新型的神经保护和认知增强分子，类黄酮非塞酮。非瑟酮不仅具有直接的抗氧化活性，还能增加细胞内主要抗氧化剂谷胱甘肽的水平。非瑟酮还能激活关键的神经营养因子信号通路。此外，它对小胶质细胞具有抗炎活性，抑制脂氧合酶的活性，从而减少促炎类二十烷酸及其副产物的产生。这种广泛的作用表明，非瑟酮有能力减少与年龄相关的神经系统疾病对脑功能的影响。
It is becoming increasingly clear that neurological diseases are multi-factorial involving disruptions in multiple cellular systems. Thus, while each disease has its own initiating mechanisms and pathologies, certain common pathways appear to be involved in most, if not all, neurological diseases described to date. Thus, it is unlikely that modulating only a single factor will be effective at either preventing disease development or slowing disease progression. A better approach is to identify small (< 900 daltons) molecules that have multiple biological activities relevant to the maintenance of brain function. Over the last few years, we have identified an orally active, novel neuroprotective and cognition-enhancing molecule, the flavonoid fisetin. Fisetin not only has direct antioxidant activity but it can also increase the intracellular levels of glutathione, the major intracellular antioxidant. Fisetin can also activate key neurotrophic factor signaling pathways. In addition, it has anti-inflammatory activity against microglial cells and inhibits the activity of lipoxygenases, thereby reducing the production of pro-inflammatory eicosanoids and their by-products. This wide range of actions suggests that fisetin has the ability to reduce the impact of age-related neurological diseases on brain function.