Role of Protease Inhibitor for Senile Plaque Formation

蛋白酶抑制剂对老年斑形成的作用

• 批准号: 02454294
• 负责人: MIYOSHI Koho
• 金额: $ 1.6万
• 依托单位: Hyogo College of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02454294/
• 关键词: Protease Inhibitor; Leupeptin; E-64; Neuritic Plaques; Alzheimer's Disease; Alpha-1-antichymotrypsin; Neuroaxonal Changes; Learning Impairment

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.

1.脑室内注射酶抑制剂亮肽素和E-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元斑块中神经元的变化非常相似。结论：1.α-1-抗糜蛋白酶，一种蛋白水解酶抑制物，免疫组织化学显示在神经炎斑块中，可引起大鼠脊髓中特征性的神经轴突改变。亮肽素对培养的神经细胞轴突的增殖有刺激作用，也有毒性作用。脑室注射蛋白水解酶抑制剂亮肽酶可引起大鼠被动回避实验的学习障碍，其神经轴突变化与神经元斑中淀粉样核附近的轴突变化相似。应用亮肽素引起的神经元改变导致动物学习障碍。目前的研究结果表明，在阿尔茨海默病的神经炎斑块中，蛋白水解酶抑制剂对形成特定的神经炎斑块的重要性。

项目成果

Takauchi S, Miyoshi K : Protease inhibitor, Leupeptin: "causes irreversible axonal changes in rats" In. Alzheimer's disease. Basic Mechanism, Diagnosis and Therapeutic Strategies. 505-513 (1991)

Takauchi S，Miyoshi K：蛋白酶抑制剂，Leupeptin：“引起大鼠不可逆的轴突变化”。

Takauchi,S.: "Alzheimer's and Parkinson's Diseases II:Basic and Therapeutic Strategies." Plenum, 800 (1990)

Takauchi,S.：“阿尔茨海默病和帕金森病 II：基本和治疗策略。”

三好 功峰: "Protease Inhibitor" 老年期痴呆研究会誌. 5. 22-24 (1993)

Komine Miyoshi：“蛋白酶抑制剂”老年痴呆研究会杂志 5. 22-24 (1993)。

Takauchi S, Miyoshi K : Degeneration of Neuronal: "Processes in Rats induced by the Protease Inhibitor, Leupeptin." In. Basic, Chlinical and Therapeutic Aspects of Alzheimer's and Parkinson's Disease. vol.1. 75-78 (1990)

Takauchi S、Miyoshi K：神经元变性：“蛋白酶抑制剂 Leupeptin 诱导的大鼠过程”。

Takauchi S, Ikegami K : Neurofibrillary: "change in rat brain as a long-term effect by intraventricular infusion of protease inhibitor, leupeptin" Neurobiology of Aging. 13. 108 (1992)

Takauchi S，Ikegami K：神经原纤维：“脑室内输注蛋白酶抑制剂亮肽素对大鼠大脑的长期影响”，《衰老神经生物学》。