A new molecular-based rehabilitation for neurodegenerative disease by in situ application of proteoglycan

2013 Fiscal Year Final Research Report

• Project/Area Number: 23650319
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Rehabilitation science/Welfare engineering
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: INOUE Katarzyna 東京医科歯科大学, 医歯(薬)学総合研究科, 助教 (90302877)
• Co-Investigator(Kenkyū-buntansha): YOKOYAMA Miki 東京医科歯科大学, 医歯(薬)学総合研究科, 准教授 (70191533) ; ZEREDO Jorge 東京医科歯科大学, 医歯(薬)学総合研究科, 非常勤講師 (10363459) ; KUMEI Yasuhiro 東京医科歯科大学, 医歯(薬)学総合研究科, 講師 (30161714)
• Co-Investigator(Renkei-kenkyūsha): YANAGISHITA Masaki 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (70132793) ; HASEGAWA Katsuya 独立行政法人 宇宙航空研究開発機構, 宇宙科学研究所, 開発員 (30425780)
• Project Period (FY): 2011 – 2013
• Keywords: リハビリテーション医学 / プロテオグライカン

Research Abstract

Many neurodegenerative diseases are often caused due to abnormal formation of protein aggregates by transglutaminase 2 (TG2). Heparan sulfate proteoglycan (HSPG) has been also suggested to play critical role in many neurodegenerative diseases. Putative interaction of TG2 with HSPG has been suggested. The purpose of this study was to determine the role of HSPG species expressed by glial cells in cell-surface trafficking and biological activity of TG2 related to pathogenesis of neurodegeneration using an in vitro approach. Subcellular fractionation and immunocytochemical analyses showed that TG2-specific compartments were also specific for HSPGs suggesting possible interaction between those molecules. Understanding the bases of molecular interaction between TG2 and HSPGs and the precise role of HSPGs in regulation of biological activity of TG2 will help to identify the pathogenic mechanism of neurodegenerative diseases and to develop targeted rational therapy.

Research Products

• [Journal Article] Tetrameric interaction of the ectoenzyme CD38 on the cell surface enables its catalytic and raft association activities (2012)
  • Author(s): Miki Hara-Y okoyama, Mutsuko Kukimoto-Niino, Kazue T erasawa, Satoru Harumiya, Katarzyna A. Podyma-Inoue, Nobumasa Hino, Kensaku Sakamoto, Satsuki Itoh, Noritaka Hashii, Y oko Hiruta, Nana Kawasaki, Chiemi Mishima-Tsumagari, Y oko Kaitsu, T omoko Matsumoto, Motoaki Wakiyama, Mikako Shirouzu, Takeshi Kasama, Hiroshi Takayanagi, Naoko Utsunomiya-Tate, Kiyoshi Takatsu, T oshiaki Katada, Y oshio Hirabayashi, Shigeyuki Y okoyama, and Masaki Y anagishita
  • Journal Title: Structure Volume: Vol.20, No.9 Pages: 1585-1595
  • DOI: 10.1016/j.str.2012.06.017
  • Peer Reviewed
• [Presentation] Role of heparan sulfate proteoglycan in etiology of neurodegenerative disease (2014)
  • Author(s): Katarzyna A. Inoue
  • Organizer: 第21回プロテオグライカンフォーラム
  • Place of Presentation: 東京都, 東京医科歯科大学
  • Year and Date: 2014-01-12
• [Presentation] Cell surface heparan sulfate proteoglycans expressed by glioma cells : biochemical characterization (2013)
  • Author(s): Katarzyna A. Inoue, Miki Y okoyama, and Masaki Yanagishita
  • Organizer: The 8th International Conference on Proteoglycans
  • Place of Presentation: Frankfurkt aim Main, Germany
  • Year and Date: 20130825-29
• [Presentation] Association of heparan sulfate proteoglycans with trypsin-accessible membrane domains (2012)
  • Author(s): Katarzyna A. Inoue, Miki Y okoyama, and Masaki Y anagishita
  • Organizer: The Gordon Research Conference on Proteoglycans
  • Place of Presentation: Proctor Academy , Andover , USA
  • Year and Date: 20120708-13
• [Presentation] Characterization of membrane rafts enriched in cell surface heparan sulfate proteoglycans isolated from a rat parathyroid cell line (2011)
  • Author(s): Katarzyna A. Inoue, Miki Y okoyama, and Masaki Y anagishita
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都市, 国立京都国際会館
  • Year and Date: 20110921-24