脳虚血の新しい治療手段としての蛋白質導入法の応用

蛋白导入法作为脑缺血新疗法的应用

• 批准号: 17659488
• 负责人: 牛島 一男
• 金额: $ 1.22万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Exploratory Research
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17659488/
• 关键词: 蛋白質導入法; 血液脳関門; 虚血性神経細胞死; TAT protein; 脳保護物質

蛋白質導入法(protein transduction)は,外来性の蛋白質を細胞内に直接輸送する方法で,血液脳関門の存在故に従来不可能であった蛋白質脳内投与の問題を解決し,脳虚血の病態解析や新しい治療法の開発に繋がる可能性を有す。11個のアミノ酸から成るペプチド(protein transduction domain,PTD)に蛋白質を結合させ,それを適度に変性させたものを全身投与し,脳を含む生体内各組織の細胞内に導入する。導入する蛋白質として,catalase, superoxide dismutase, glutathione peroxidase, neuroglobin, hypoxia inducible factor, erythropoietin, heat shock protein, nitric oxide synthases, poly(ADP ribose)polymerase, neurtrophic factors, proto-oncogene productsなどを検討する。現在,そのいくつかについてcomplementary DNAを作成し,PTD融合蛋白質用の発現プラスミドにそれらを取り込んでいる。今後,大腸菌に導入し,大腸菌を用いた蛋白質合成を行い,さらに蛋白質を変性・分離精製し,培養神経細胞や生体ラットに導入する。脳虚血モデル(middle cerebral artery occlusion,4-vessel occlusion, oxygen glucose deprivation)を用いて,導入された蛋白質の神経細胞保護効果を検討する。

Protein introduction method (protein transduction), the method of direct transport of foreign proteins into cells, and the existence of blood barrier, so it cannot be transported It is possible that the problem of internal administration of protein can be solved, and there is a possibility that the pathological analysis of blood deficiency and new treatment methods can be solved. 11 protein transduction domain, PTD), it is a protein that binds to it, it has a moderate resistance to it, it is administered to the whole body, and it is introduced into the cells of various tissues in the body. Import するproteinとして, catalase, superoxide dismutase, glutathione peroxidase, neuroglobin, hypoxia inducible factor, erythropoietin, heat shock protein, nitric oxide synthases, poly(ADP ribose)polymerase, neurtrophic factors, proto-oncogene productsなどを検曰する. Nowadays, そのいくつかについてcomplementary DNA is made, and the PTD fusion protein is made of の発成プラスミドにそれらをtaken by り込んでいる. In the future, coliform bacteria will be introduced, coliform protein synthesis will be carried out, protein properties, separation and purification will be carried out, and neurobiology of cultured cells will be introduced. It is used to treat middle cerebral artery occlusion, 4-vessel occlusion, and oxygen glucose deprivation, and introduce the protein into it to protect cells.