Modified enzyme which target to neuronal cells to cross blood brain barrier

修饰酶靶向神经元细胞穿过血脑屏障

• 批准号: 02557042
• 负责人: ETO Yoshikatsu
• 金额: $ 3.26万
• 依托单位: Tokyo Jikei University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02557042/
• 关键词: liposome; blood brain barrier; neuronal cell; mannnose terminal; Glucocerebrosidase; リボゾ-ム; グリア細胞; cerebrosideβ-galactosidase; マンノ-ス; リポゾ-ム; 脳障害; 酵素補充療法; α_2ーマクログロブリン; 培養神経細胞; αーマンノ-ス含有リポゾ-ム

MODIFIED ENZYME WHICH TARGFRS TO NEURONAL CELLS TO CROSS BLOOD BRAIN BARRIERWe tried to prepare modified placental glucocerebrosidase treated with neuraminidase and galactosidase and mumose terminal glucocerebrosidase was injected intravenously into mouse. We chased enzyme activities of glucocerebrosidase in mouse brain, Ever, kidney and other tissues. The maximum activity of the enzyme was obtkned after 15 minute injection, and significant staining of-enzyme-activity was found in the brain. These data suggest that mamose terminated enyzme could be useful for the treatment of neuronopathic Gaucher disease. Liposomes prepared from lecithincholesterol- aminophenylmwmoside (7 : 2 : 1) were efficiently incorporated into mouse brain across the blood brain barrier. Furthermore, hposomes injected intraperitoneauy were exclussively distributed into lysosome rich fraction and taken up by glial cells. These data suggest that blood brain barrier cells and glial cells recognize mannose and can be used for the treattnent of brain damage by lysosomat storage disease.

以神经氨酸酶和半乳糖苷酶为处理手段制备胎盘糖脑苷酶修饰物，并将其静脉注射小鼠。我们对小鼠脑、肝、肾等组织中葡萄糖脑苷酶的活性进行了测定。注射15分钟后酶活性达到最大值，脑内酶活性染色明显。这些数据提示乳腺终止酶可用于神经病变戈谢病的治疗。由卵磷脂-胆固醇-氨基苯基莫苷（7:2:1）制备的脂质体可通过血脑屏障有效地进入小鼠大脑。此外，腹腔注射的小体排他性地分布在富含溶酶体的部分，并被胶质细胞吸收。这些数据表明，血脑屏障细胞和神经胶质细胞能够识别甘露糖，并可用于治疗溶酶体储存病引起的脑损伤。

项目成果

Kawame H.,Eto Y.: "A New Glucocerebrosidase-Gene Missense Mutation Responsible for Neuronopathic Gacher Disease in Japanese Datients." Am.J Hum Genet. 49. 1378-1380 (1991)

Kawame H.，Eto Y.：“一种新的葡萄糖脑苷脂酶基因错义突变导致日本患者的神经病性盖赫病。”

Sugama S., Kim S. U., Ida H, and Eto Y.: "Psychosine cytotoxicity in rat neural cell cultures and protection by phorbol ester and olimethyl sulfoxide." Pediatr. Res.28. 473-476 (1990)

Sugama S.、Kim S. U.、Ida H 和 Eto Y.：“大鼠神经细胞培养物中的精神苷细胞毒性以及佛波酯和寡甲基亚砜的保护。”

Tahara T., Kraus J. P. and Rosengerg L. E.: "Direct DNA sequencing of PCR amplified genomic DNA by the Maxam-Gilbert method." Bio Technique. 8. 366-368 (1990)

Tahara T.、Kraus J. P. 和 Rosengerg L. E.：“通过 Maxam-Gilbert 方法对 PCR 扩增的基因组 DNA 进行直接 DNA 测序。”

Ida H,Eto Y.: "Biochemical and Morphological studies of dorsal root ganglion and its cultured from twitcher mouse." Brain and Develop.12. 412-416 (1990)

Ida H，Eto Y.：“背根神经节及其培养物的生化和形态学研究。”

Y. Eto, F. Umezawa: "Iposomal therapy in lysosomal storage disease." Amer. J. Med. Genet.7. 85-88 (1989)

Y. Eto，F. Umezawa：“溶酶体贮积病的脂质体疗法。”