Neuroprotective actions of selective estrogen receptor modulators.
Neuroprotective actions of selective estrogen receptor modulators.
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DOI：
10.1016/j.psyneuen.2009.04.012
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发表时间：
2009-12
影响因子：
3.7
通讯作者：
Garcia-Segura, Luis M
中科院分区：
文献类型：
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作者：
DonCarlos, Lydia L;Azcoitia, Inigo;Garcia-Segura, Luis M
随着年龄的增长，性激素水平下降可能对大脑功能产生负面影响，因为这种下降与神经退行性疾病的进展，抑郁症状增加和其他心理障碍有关。来自动物研究的大量证据表明，性类固醇，特别是雌二醇，具有神经保护作用。然而，雌二醇治疗对大脑的潜在益处被周围的负面、危及生命的风险所抵消。促进神经保护的潜在治疗替代方案是使用选择性雌激素受体调节剂（SERM），其可以被设计为在脑中而不是在其他器官中以组织选择性作为雌激素受体激动剂起作用。目前可用的SERM不仅具有组织选择性，而且具有脑内的细胞选择性，并且差异地调节小胶质细胞、星形胶质细胞和神经元的活化。最后，SERM可以促进雌激素受体与生长因子的神经保护信号的相互作用，例如磷脂酰肌醇3-激酶/糖原合成酶激酶3途径。
Decreasing levels of sex hormones with aging may have a negative impact on brain function, since this decrease is associated with the progression of neurodegenerative disorders, increased depressive symptoms and other psychological disturbances. Extensive evidence from animal studies indicates that sex steroids, in particular estradiol, are neuroprotective. However, the potential benefits of estradiol therapy for the brain are counterbalanced by negative, life-threatening risks in the periphery. A potential therapeutic alternative to promote neuroprotection is the use of selective estrogen receptor modulators (SERMs), which may be designed to act with tissue selectivity as estrogen receptor agonists in the brain and not in other organs. Currently available SERMs act not only with tissue selectivity, but also with cellular selectivity within the brain and differentially modulate the activation of microglia, astroglia and neurons. Finally, SERMs may promote the interaction of estrogen receptors with the neuroprotective signaling of growth factors, such as the phosphatidylinositol 3-kinase/glycogen synthase kinase 3 pathway.