Therapeutic principles on protein misfolding diseases

蛋白质错误折叠疾病的治疗原则

• 批准号: 19390045
• 负责人: KAI Hirofumi
• 金额: $ 12.15万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19390045/
• 关键词: 薬理学; タンパク質; 遺伝病; cystic fibrosis; FAP; CFTR; transthyretin; phosphatidic acid; mucin; 小胞体; アミロイド; ENaC; 嚢胞性線維症(CF); 家族性アミロイドポリニューロパチー(FAP); calnexin(CNX); transthyretin(TTR); 小胞体関連分解(ERAD); BiP; calnexin; toll-like receptor

Drug development for cystic fibrosis and familial amyloid polyneuropathy is still in progress. We found out the intracellular protein quality control mechanisms of ΔF508 CFTR, a major mutant of cystic fibrosis, and of transthyretin variants, resulting in proposal of new concept of drug development for familial amyloid polyneuropathy. In addition, we found that the endoplasmic reticulum-associated degradation of transthyretin variants is negatively regulated by BiP in mammalian cells.

治疗囊性纤维化和家族性淀粉样多发性神经病的药物开发仍在进行中。我们发现了囊性纤维化的主要突变体ΔF508cftr和转甲状腺素变异体的细胞内蛋白质质量控制机制，从而提出了治疗家族性淀粉样多发性神经病的药物开发的新概念。此外，我们还发现，在哺乳动物细胞中，转甲状腺素变异体的内质网相关降解受到Bip的负调控。

项目成果

TLR3 induction by anticancer drugs potentiates poly I:C‐induced tumor cell apoptosis

• DOI: 10.1111/j.1349-7006.2010.01567.x
• 发表时间: 2010-07
• 期刊: Cancer Science
• 影响因子: 5.7
• 作者: M. Taura;Ryosuke Fukuda;M. Suico;Ayaka Eguma;Tomoaki Koga;T. Shuto;Takashi Sato;Saori Morino-Koga;H. Kai

The role of coat protein complex II machinery on the secretion, endoplasmic reticulum retention and endoplasmic reticulum-associated degradation of transthyretin

外壳蛋白复合物 II 机制对甲状腺素运载蛋白分泌、内质网保留和内质网相关降解的作用

• 发表时间: 2008
• 作者: M.Miyata;T.Sato;M.Mizuguchi;T.Nakamura;S.Ikemizu;Y,Nabeshima;S.Susuki;Y.Suwa;H.Morioka;Y.Ando;M.A.Suico;T.Shuto;T.koga;Y.Yamagata;H.Kai;Takashi Sato
• 通讯作者: Takashi Sato

Mild Electrical Stimulation Increases Ubiquitinated Proteins and Hsp72 in A549 Cells via Attenuation of Proteasomal Degredation

轻度电刺激通过减弱蛋白酶体降解增加 A549 细胞中的泛素化蛋白和 Hsp72

• 发表时间: 2008
• 期刊: J Pharmacol Sci. 108
• 作者: Saori Morino;Mary Ann Suico;Tatsuya Kondo;Erika Sekimoto;Shuichiro Yano. Tomoko Matsuda;Takashi Matsuno;Tsuyoshi Shuto;Eiichi Araki;Hirohumi Kai
• 通讯作者: Hirohumi Kai

Calreticulin positively regulates the expression and function of epithelial sodium channel

• DOI: 10.1016/j.yexcr.2009.09.023
• 发表时间: 2009-11-15
• 期刊: EXPERIMENTAL CELL RESEARCH
• 影响因子: 3.7
• 作者: Sugahara, Takuya;Koga, Tomoaki;Kai, Hirofumi
• 通讯作者: Kai, Hirofumi

Mild Electrical Stimulation with heat shock ameliorates insulin resistance via enhanced insulin signaling. Increases Ubiquitinated Proteins and Hsp72 in A549 Cells via Attenuation of Proteasomal Degredation.

热休克的温和电刺激可通过增强胰岛素信号传导来改善胰岛素抵抗。

• 发表时间: 2008
• 期刊: PLoS ONE 3(12)
• 作者: Morino S;et al.
• 通讯作者: et al.