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

通过原位应用蛋白多糖进行神经退行性疾病的新型分子康复

• 批准号: 23650319
• 负责人: INOUE Katarzyna
• 金额: $ 2.33万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23650319/
• 关键词: リハビリテーション医学; プロテオグライカン

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.

许多神经退行性疾病通常是由于转氨酶2（TG 2）引起的蛋白质聚集体的异常形成而引起的。硫酸乙酰肝素蛋白聚糖（HSPG）也被认为在许多神经退行性疾病中起关键作用。已经提出了TG2与HSPG的假定相互作用。本研究的目的是确定神经胶质细胞表达的HSPG种类在细胞表面运输中的作用以及使用体外方法与神经变性发病机制相关的TG2的生物活性。亚细胞分级分离和免疫细胞化学分析表明，TG2特异性车厢也表明这些分子之间可能的相互作用的HSPGs。了解TG 2与HSPGs相互作用的分子基础以及HSPGs在调节TG 2生物学活性中的确切作用，将有助于阐明神经退行性疾病的发病机制，并制定针对性的合理治疗方案。

项目成果

Cell surface heparan sulfate proteoglycans expressed by glioma cells : biochemical characterization

神经胶质瘤细胞表达的细胞表面硫酸乙酰肝素蛋白聚糖：生化特征

• 发表时间: 2013
• 作者: Katarzyna A. Inoue;Miki Y okoyama;and Masaki Yanagishita
• 通讯作者: and Masaki Yanagishita

Cell surface heparan sulfate proteoglycans expressed by glioma cells: biochemical characterization.

神经胶质瘤细胞表达的细胞表面硫酸乙酰肝素蛋白聚糖：生化特征。

• 发表时间: 2013
• 作者: Katarzyna A. Podyma-Inoue;Miki Yokoyama and Masaki Yanagishita
• 通讯作者: Miki Yokoyama and Masaki Yanagishita

Association of heparan sulfate proteoglycans with trypsin-accessible membrane domains

硫酸乙酰肝素蛋白多糖与胰蛋白酶可及膜域的关联

• 发表时间: 2012
• 作者: Katarzyna A. Inoue;Miki Y okoyama;and Masaki Y anagishita
• 通讯作者: and Masaki Y anagishita

Tetrameric Interaction of the Ectoenzyme CD38 on the Cell Surface Enables Its Catalytic and Raft-Association Activities

• DOI: 10.1016/j.str.2012.06.017
• 发表时间: 2012-09-05
• 期刊: STRUCTURE
• 影响因子: 5.7
• 作者: Hara-Yokoyama, Miki;Kukimoto-Niino, Mutsuko;Yanagishita, Masaki
• 通讯作者: Yanagishita, Masaki

Role of heparan sulfate proteoglycan in etiology of neurodegenerative disease

硫酸乙酰肝素蛋白多糖在神经退行性疾病病因学中的作用

• 发表时间: 2014
• 作者: 金榮鎭 ;荏原充宏 ;青柳隆夫;Katarzyna A. Inoue
• 通讯作者: Katarzyna A. Inoue