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.97.7.3602
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发表时间：
2000-03
影响因子：
11.1
通讯作者：
R. Bi;G. Broutman;M. Foy;Richard F. Thompson;Michel Baudry
中科院分区：
文献类型：
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作者：
R. Bi;G. Broutman;M. Foy;Richard F. Thompson;Michel Baudry
女性雌激素替代疗法与改善认知缺陷和降低阿尔茨海默病的发病率有关。本研究表明雌激素对 N-甲基-d-天冬氨酸 (NMDA) 和红藻氨酸介导的神经毒性具有神经保护作用，这是由酪氨酸激酶/丝裂原激活蛋白激酶 (MAPK) 途径介导的作用。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，雌激素介导的海马切片长时程增强是通过 src 酪氨酸激酶途径的激活介导的。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 NMDA 受体功能和长期增强作用，又保留针对兴奋性毒性的神经保护特性。这些发现值得进一步评估雌激素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。
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.