RELEASE OF ALZHEIMER AMYLOID PRECURSOR DERIVATIVES STIMULATED BY ACTIVATION OF MUSCARINIC ACETYLCHOLINE-RECEPTORS
RELEASE OF ALZHEIMER AMYLOID PRECURSOR DERIVATIVES STIMULATED BY ACTIVATION OF MUSCARINIC ACETYLCHOLINE-RECEPTORS
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DOI：
10.1126/science.1411529
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发表时间：
1992-10-09
期刊：
影响因子：
56.9
通讯作者：
GROWDON, JH
中科院分区：
文献类型：
--
作者：
NITSCH, RM;SLACK, BE;GROWDON, JH
淀粉样前体蛋白（APP）加工过程的改变是阿尔茨海默病患者大脑中淀粉样沉积物形成的核心事件。为了研究细胞 APP 处理是否受细胞表面神经递质受体控制，用人脑毒蕈碱乙酰胆碱受体基因转染人胚胎肾 (293) 细胞系。用卡巴胆碱刺激 m1 和 m3 受体亚型可在治疗几分钟内增加 APP 衍生物的基础释放，表明预先存在的 APP 是响应受体激活而释放的。受体激活的 APP 释放被星形孢菌素阻断，表明蛋白激酶介导神经递质受体控制的 APP 处理。
Altered processing of the amyloid precursor protein (APP) is a central event in the formation of amyloid deposits in the brains of individuals with Alzheimer's disease. To investigate whether cellular APP processing is controlled by cell-surface neurotransmitter receptors, human embryonic kidney (293) cell lines were transfected with the genes for human brain muscarinic acetylcholine receptors. Stimulation of m1 and m3 receptor subtypes with carbachol increased the basal release of APP derivatives within minutes of treatment, indicating that preexisting APP is released in response to receptor activation. Receptor-activated APP release was blocked by staurosporine, suggesting that protein kinases mediate neurotransmitter receptor-controlled APP processing.