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

The Implications of TDP-43 Mutations in Pathogenesis of Amyotrophic Lateral Sclerosis Tomohiko Ishihara 1,2 , Akio Yokoseki 1 , Masatoyo Nishizawa 1 , Hitoshi Takahashi 3 , Osamu Onodera 2 1Department of Neurology,Brain Research Institute,Niigata University 2Department of Molecular Neuroscience,Center for Bioresource-based Researches,Brain Research Institute,Niigata University 3Department of Pathology,Center for Bioresource-based Researches,Brain Research Institute,Niigata University Keyword: TAR DNA binding protein 43 kDa (TDP-43) , hnRNP , missense mutation , amyotrophic lateral sclerosis (ALS)-10 pp.1301-1307
Published Date 2009/11/1
DOI https://doi.org/10.11477/mf.1416100591
  • Abstract
  • Look Inside
  • Reference

Abstract

 The molecular pathogenesis of amyotrophic lateral sclerosis (ALS) is unclear. TAR DNA-binding proteins of 43 kDa (TDP-43) -positive-cytoplasmic inclusions have been found in the glia and neurons of ALS patients. TDP-43 -positive inclusions have been reported in several neurodegenerative disorders other than ALS. Therefore it is not clear whether TDP-43 plays a primary role in the pathogenesis of ALS. The discovery of TDP-43 mutations in ALS patients indicates that TDP-43 plays a pivotal role in the pathogenesis of ALS. More than 30 mutations in the TDP-43 gene have been identified in patients with familial and sporadic ALS. ALS with a TDP-43 mutation is classified as ALS-10. The clinical features of ALS-10 are quite similar to those of sporadic ALS. Furthermore,the neuropathological findings for ALS-10,including TDP-43 -positive inclusions and Bunina bodies,are identical to those in sporadic ALS; these findings indicate that the study of ALS-10 may lead to a better understanding of sporadic ALS. Most of the mutations are located in the C-terminus of TDP-43,which may function as a binding domain for heterogeneous nuclear ribonucleoprotein. Biochemical analyses of TDP-43 in sporadic ALS patients indicate that the TDP-43 is truncated,and the C-terminus is phosphorylated forming insoluble inclusions in the neurons and glia. In certain ALS-10 cases,missense mutated TDP-43s tend to be truncated and form inclusions. The cytotoxicity of these mutated TDP-43s has also been reported; however,these results are still controversial. Therefore,further analysis is required to elucidate the molecular mechanism underlying the development of ALS-10.


Copyright © 2009, 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

もっと見る

文献を共有