The processing of the amyloid precursor protein (APP) has become a major focus of research into Alzheimer's disease (AD). Recently, repeated doses of testosterone have been shown to enhance the secretion of the product of the alpha-cleavage pathway of APP (sAPPalpha) over a period of days. Here, the time course of secretion of sAPPalpha after a single physiological dose of testosterone using an immortalized rat hypothalamic cell line (GT1-7) and the signalling pathways involved was analyzed. Testosterone was found to increase the amount of APP secretion rapidly after treatment without effecting the overall amount of cellular APP. The species of APP secreted was found to be predominantly the product of the non-amyloidogenic alpha-secretory pathway. Further, this event is regulated via aromatase-mediated conversion of testosterone to estrogen and the mitogen-activated protein kinase (MAP kinase) signalling pathway. Taken together these data partially elucidates the cellular cascade by which testosterone stimulates sAPP secretion.

译文

:淀粉样蛋白前体蛋白(APP)的加工已成为阿尔茨海默氏病(AD)研究的主要重点。最近,已显示重复剂量的睾丸激素可在几天内增强APP(sAPPalpha)的alpha裂解途径的产物的分泌。在这里,分析了使用永生化的大鼠下丘脑细胞系(GT1-7)进行单次生理剂量的睾丸激素分泌后sAPPalpha分泌的时程和涉及的信号通路。发现睾丸激素可在治疗后迅速增加APP分泌​​量,而不会影响细胞APP的总量。发现分泌的APP种类主要是非淀粉样生成的α分泌途径的产物。此外,该事件是通过芳香酶介导的睾丸激素向雌激素的转化以及有丝分裂原激活的蛋白激酶(MAP激酶)信号传导途径来调节的。这些数据加在一起,部分阐明了睾丸激素刺激sAPP分泌​​的细胞级联反应。

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