The tyrosine kinase and mitogen-activated protein kinase pathways mediate multiple effects of estrogen in hippocampus
The tyrosine kinase and mitogen-activated protein kinase pathways mediate multiple effects of estrogen in hippocampus
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DOI：
10.1073/pnas.060034497
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发表时间：
2000-03-28
影响因子：
11.1
通讯作者：
Baudry, M
中科院分区：
文献类型：
--
作者：
Bi, RF;Broutman, G;Baudry, M
女性的雌激素替代疗法与认知缺陷的改善和阿尔茨海默病的发病率降低有关。目前的研究表明，雌激素对N-甲基-D-天冬氨酸(NMDA)和海人藻氨酸(KA)介导的神经毒性具有神经保护作用，这种保护作用是通过酪氨酸激酶/丝裂原活化蛋白激酶(MAPK)途径实现的。雌激素还通过src酪氨酸激酶/MAPK途径刺激NMDA受体的酪氨酸磷酸化。最后，雌激素介导的海马片长时程增强是通过激活src酪氨酸激酶通路来实现的。因此，雌激素通过激活src酪氨酸激酶和细胞外信号相关蛋白激酶/MAPK信号通路，既增强了NMDA受体的功能，又增强了长期增强作用，并保留了针对兴奋性毒性的神经保护特性。这些发现为进一步评估雌激素类化合物治疗阿尔茨海默病和其他神经退行性疾病的有效性提供了依据。
Estrogen replacement therapy in women is associated with improvement of cognitive deficits and reduced incidence of Alzheimer's disease. The present study indicates that estrogen is neuroprotective against N-methyl-D-aspartate (NMDA)- and kainate-mediated neurotoxicity, an effect mediated by tyrosine kinase/mitogen-activated protein kinase (MAPK) pathways. Estrogen also stimulates tyrosine phosphorylation of NMDA receptors via an src tyrosine kinase/MAPK pathway. Finally, estrogen-mediated enhancement of long-term potentiation in hippocampal slices is mediated by activation of an src tyrosine kinase pathway. Thus, estrogen, by activating an src tyrosine kinase and the extracellular signal-related protein kinase/MAPK signaling pathway, both enhances NMDA receptor function and long-term potentiation and retains neuroprotective properties against excitotoxicity. These findings warrant further evaluation of the usefulness of estrogenic compounds for the treatment of Alzheimer's disease and other neurodegenerative diseases.