Molecular pathogenesis of familial encephalopathy with neuroserpin inclusion bodies

2008 Fiscal Year Final Research Report

• Project/Area Number: 18590285
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: University of Toyama
• Principal Investigator: HIRAGA Koichi University of Toyama, 大学院・医学薬学研究部, 教授 (40004733)
• Co-Investigator(Kenkyū-buntansha): KATO Ichiro 富山大学, 大学院・医学薬学研究部, 准教授 (50250741) ; KAWAGUCHI Hiroshi 富山大学, 大学院・医学薬学研究部, 助教 (50361952)
• Project Period (FY): 2006 – 2008
• Keywords: 変異ニューロセルピン / 免疫電顕 / 封入体形成機構 / 小胞体 / リソゾーム

Research Abstract

変異型神経特異的セリンプロテアーゼインヒビタ=(ニューロセルピン)は家族性ニューロセルピン封入体脳症の原因となる。数種の変異型ヒトニューロセルピンが知られているが、今回、人では最も劇症型を起こすと言われるG392Eニューロセルピンをニューロンでのみ発現するトランスジェニックマウスを作製し、変異型ニューロセルピンのニューロン内蓄積機構とその結果起こるニューロンの機能障害の原因を追及した。その結果、変異型ニューロセルピンは発現量、変異部位、加齢に依存してニューロン小胞体とリソゾームに蓄積し、代謝分解量を超える合成量が有れば、加齢と共に病的変化を起こすことを明らかにした。

Research Products

• [Journal Article] Genomic organization of regions that regulate chicken glycine decarboxylase gene transcription: physiological and pathological implications (2009)
  • Author(s): Kawaguchi H., Okamoto, S., Sikdar, D., Kume, A., Li. F., Mohafez, O.M.M., Shehata, M.H., and Hiraga, K
  • Journal Title: Gene 432 Pages: 7-18
  • Peer Reviewed
• [Journal Article] Glycine cleavage system : reaction mechanism, physiological significance, and hyperglycinemia (2008)
  • Author(s): Kikuchi, G., Motokawa, Y., Yoshida, T., and Hiraga, K
  • Journal Title: Proc. JPN. Acad., Ser. B 84 Pages: 246-263
  • Peer Reviewed
• [Journal Article] A novel model of insulin-dependent diabetes with renal and retinal lesions by transgenic expression of CaMKII (Thr286Asp) in pancreatic -cells. Diabetes Metab (2008)
  • Author(s): Kato I., Oya, T., Suzuki, H., Takasawa, K., Ichsan, A.M., Nakada, S., Ishii, Y., Shimada, Y., Sasahara, M., Tobe, K., Takasawa, S., Okamoto, H., Hiraga, K
  • Journal Title: Res. Rev 24 Pages: 486-497
  • Peer Reviewed
• [Journal Article] Mutation-, aging-, and gene dosage-dependent accumulation of neuroserpin (G392E) in endoplasmic reticula and lysosomes of neurons in transgenic mice (2008)
  • Author(s): Takasawa, A., Kato, I., Takasawa, K., Ishii, Y., Yoshida, T., Shehata, M.H., Kawaguchi, H.,Mohafez, O.M.M., Sasahara, M., and Hiraga, K
  • Journal Title: J. Biol. Chem 283 Pages: 35606-35613
  • Peer Reviewed
• [Journal Article] Nonalcoholic steatohepatitis and hepatocellular carcinoma in galectin-3 knockout mice (2008)
  • Author(s): Nakanishi, Y., Tsuneyama, K., Nomoto, K., Fujimoto, M., Salunga, T.L., Nakajima, T., Miwa, S., Murai,Y., Hayashi, S., Kato, I., Hiraga, K., Hsu, D.K., Liu, F-T., and Takano, Y
  • Journal Title: Hepatol. Res 38 Pages: 1241-152
  • Peer Reviewed
• [Journal Article] Novel transcript profiling of diffuse alveolar damage induced by hyperoxia exposure in mice: normalization by glyceraldehydes-3 phosphate dehydrogenase (2008)
  • Author(s): Shimada, I., Matsui, K., Brinkmann, B., Hoh,o.ff., .C., Hiraga, K., Tabuchi, Y., Takasaki, I., Kato, I., Kawaguchi, H., Takasawa, K., Iida, R., Takizawa, H., Matsuki, T
  • Journal Title: Int. J. Legal Med 122 Pages: 373-383
  • Peer Reviewed
• [Journal Article] Targeted disruption of the galectin-3 gene results in decreased susceptibility to NNK-induced lung tumorigenesis: an oligonucleotide microarray studyJ (2008)
  • Author(s): Abdel-Aziz H. O., Murai, Y., Takasaki, I., Tabuchi, Y., Zheng, H-C., Nomoto, K., Takahashi, H., Tsuneyama, K., Kato, I., Hsu, D.K., Liu, F-T., Hiraga, K., and Takano, Y
  • Journal Title: Cancer Res. Clin. Oncol 134 Pages: 777-788
  • Peer Reviewed
• [Journal Article] Transcriptional modulation by nuclear matrix protein P130/MAT3 associated with MAR/SAR. (2007)
  • Author(s): Hibino, Y., Usui, T., & Hiraga, K
  • Journal Title: In Nuclear Dynamics, Nagata, K., & Takeyasu, K. eds Pages: 255-262
  • Peer Reviewed
• [Journal Article] Neuroprotective role of transgenic PAF-acetyl hydrolase II in mouse models of focal cerebral ischemia (2007)
  • Author(s): Umemura, K., Kato, I., Hirashima, Y., Ishii, Y., Inoue, T., Aoki, J., Kono, K., Oya, T., Hayashi, N., Hamada, H., Endo, S., Oda, M., Arai, H., Kinouchi, H., and Hiraga, K
  • Journal Title: Stroke 38 Pages: 1063-1068
  • Peer Reviewed
• [Presentation] CCl_4障害肝に誘導されるガレクチ-3の役割 (2008)
  • Author(s): 川口博、高畑正裕、張鴻、常山耕一、鄭華川、平賀紘一
  • Organizer: BMB2008(第31回日本分子生物学会年会、第81回日本生化学会大会合同大会)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] 家族性早期発症型認知症FENIBモデルマウスにおいて変異型ニューロセルピン(G397E)は小胞体とリソゾームに蓄積する (2007)
  • Author(s): 加藤一郎
  • Organizer: BMB2007(日本生化学会、日本分子生物学会合同年会)
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13