Koistinaho J, Pyykönen I, Keinänen R, Hökfelt T
A.I. Virtanen Institute, University of Kuopio, Finland.
Neuroreport. 1996 Nov 4;7(15-17):2727-31. doi: 10.1097/00001756-199611040-00064.
beta-Amyloid precursor protein (beta APP) can be alternatively processed to result in release of either neurotoxic amyloid beta-peptide, or secreted forms of beta APP, which might have a role in neuronal plasticity and survival. Four different forms of beta APP mRNAs have been described in rodents: APP695, APP714, APP751 and APP770. The two larger forms contain a Kunitz-type serine protease inhibitor domain (KPI). Since previous studies have shown increased APP immunoreactivity following brain ischaemia, we used in situ hybridization histochemistry to determine whether induction of any APP mRNA transcripts take place following focal brain ischaemia. While the hybridization signal of all APP isoforms in the infarct was lost 4-24 h following the insult, APP770 mRNA was slightly upregulated in the ipsilateral cortex and striatum 3 days after 90 min ischaemia. At 7 days post-ischaemia APP770 and APP751 mRNAs were induced in the infarct core and in a thin perifocal zone. KPI-containing APP forms are differentially induced following focal brain ischaemia, possibly as a neuroprotective response to neuronal injury.
β-淀粉样前体蛋白（β-APP）可以通过不同的加工方式，释放出具有神经毒性的β-淀粉样肽，或者分泌型β-APP，后者可能在神经元可塑性和存活中发挥作用。在啮齿动物中已发现四种不同形式的β-APP信使核糖核酸：APP695、APP714、APP751和APP770。两种较大的形式含有一个库尼茨型丝氨酸蛋白酶抑制剂结构域（KPI）。由于先前的研究表明脑缺血后APP免疫反应性增强，我们采用原位杂交组织化学方法来确定局灶性脑缺血后是否会诱导任何APP信使核糖核酸转录本。虽然在损伤后4至24小时梗死灶中所有APP亚型的杂交信号均消失，但在90分钟缺血3天后，同侧皮质和纹状体中APP770信使核糖核酸略有上调。缺血7天后，梗死灶核心和薄的灶周区域诱导出APP770和APP751信使核糖核酸。含KPI的APP形式在局灶性脑缺血后受到不同程度的诱导，这可能是对神经元损伤的一种神经保护反应。
