Role of Protease Inhibitor for Senile Plaque Formation

1. 脑室内注射蛋白酶抑制剂、胰肽和E-64，可引起注射部位神经元轴突的肿胀和变性，这与阿尔茨海默病神经性斑块的神经元变化非常相似。α -1-抗凝乳胰蛋白酶是一种蛋白酶抑制剂，免疫组织化学研究表明，它在神经斑块中引起大鼠脊髓特征性的神经轴突改变。白细胞介素对培养的神经细胞轴突的增殖具有刺激和毒性作用。在被动回避实验中，脑室内给予蛋白酶抑制剂白细胞介素可引起明显的学习障碍。蛋白酶抑制剂诱导的神经轴突变化与神经性斑块淀粉样蛋白核心附近的轴突变化非常相似。给药后神经元的改变引起动物的学习障碍。目前的研究结果表明，蛋白酶抑制剂在阿尔茨海默病的神经性斑块中起着重要的作用。

1. Intracerebroventricular injection of protease inhibitor, leupeptin, and E-64, induced swelling and degeneration of neuronal axon in injected sites, which were closely similar to the neuronal changes in the neuritic plaques of Alzheimer's diseae. Alpha-1-antichymotrypsin, the protease inhibitor, which was demonstrated immunohistochemically in the neuritic plaques, caused characteristic neuroaxonal changes in the spinal cord in rats.2. Leupeptin showed stimulating and toxic effects of proliferation of axons in the cultured neuronal cells.3. Intracerebroventricular administration of leupeptin, protease inhibitor, caused a significant learning impairment in passive avoidance test in rats.Neuroaxonal changes, induced by protease inhibitor, were closely similar to the axonal changes in the vicinity of amyloid core in neuritic plaques. The neuronal changes by leupeptin administration caused a learning impairment in animals. Results of the present studies indicated the importance of protease inhibitor to from a specific neuritic changes in neuritic plaques in Alzheimer's disease.