雑誌文献を検索します。書籍を検索する際には「書籍検索」を選択してください。

検索

書誌情報 詳細検索 by 医中誌

Japanese

  • Abstract
  • Look Inside
  • Reference

Abstract

Protein misfolding crucially underlies the pathogenesis of amyotrophic lateral sclerosis (ALS). Mutant superoxide dismutase 1 (SOD1) and TAR DNA-binding protein 43kDa (TDP-43) are major causal proteins for familial and sporadic ALS, respectively, provoking diverse pathogenic pathways in both intracellular and extracellular environments. Of note, cell-to-cell spreading behavior is implicated in the progression of neurodegeneration, suggesting application in immunotherapies including vaccination, and antibody application as a molecular targeting therapy, due to strict antigen-specificity. Although immunotherapy of intravenous application of full-length immunoglobulin is aimed at targeting the extracellular proteins because of low access to the cytosol, it is therefore necessary to generate expression vectors for variable single chain fragments (scFv) that target intracellular proteins. Despite the advantages of scFv, such as low molecular size and the ability to apply molecular modifications adding proteolytic signals, safety and efficacy should be cautiously estimated in preclinical studies, using appropriate animal models. In ALS, we firstly succeeded in the vaccination of mutant SOD1 transgenic mice, which was followed by accumulating evidence showing the efficacy of immunization against misfolded SOD1. In TDP-43 proteinopathy, we are developing immunotherapy using intrabodies with proteolytic properties against mislocalized or aggregated forms of TDP-43 inside cells.


Copyright © 2019, Igaku-Shoin Ltd. All rights reserved.

基本情報

電子版ISSN 1344-8129 印刷版ISSN 1881-6096 医学書院

関連文献

  • ALSの病理 吉田 眞理 医学書院 BRAIN and NERVE
    71巻 11号 (2019年11月)
    pp.1152-1168
    • 有料閲覧
  • 孤発性ALSの神経生物学 陸 雄一 , 石垣 診祐 , 祖父江 元 金原一郎記念医学医療振興財団 生体の科学
    73巻 5号 (2022年10月)
    pp.472-473
    • 有料閲覧
  • ALSとFTD 渡辺 保裕 医学書院 BRAIN and NERVE
    71巻 11号 (2019年11月)
    pp.1227-1235
    • 有料閲覧
  • ALSと映像作品 荻野 美恵子 医学書院 BRAIN and NERVE
    74巻 12号 (2022年12月)
    pp.1384-1387
    • 有料閲覧
  • 家族性ALS 鈴木 直輝 , 西山 亜由美 , 加藤 昌昭 , 割田 仁 , 青木 正志 医学書院 BRAIN and NERVE
    71巻 11号 (2019年11月)
    pp.1169-1181
    • 有料閲覧
もっと見る

文献を共有