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Mechanisms Associated with TDP-43 Neurotoxicity in ALS/FTLD

  • Marc Shenouda
  • Ashley B. Zhang
  • Anna Weichert
  • Janice Robertson
Chapter
Part of the Advances in Neurobiology book series (NEUROBIOL, volume 20)

Abstract

The discovery of TDP-43 as a major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) was first made in 2006. Prior to 2006 there were only 11 publications related to TDP-43, now there are over 2000, indicating the importance of TDP-43 to unraveling the complex molecular mechanisms that underpin the pathogenesis of ALS/FTLD. Subsequent to this discovery, TDP-43 pathology was also found in other neurodegenerative diseases, including Alzheimer’s disease, the significance of which is still in the early stages of exploration. TDP-43 is a predominantly nuclear DNA/RNA-binding protein, one of a number of RNA-binding proteins that are now known to be linked with ALS/FTLD, including Fused in Sarcoma (FUS), heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), and heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1). However, what sets TDP-43 apart is the vast number of cases in which TDP-43 pathology is present, providing a point of convergence, the understanding of which could lead to broadly applicable therapeutics. Here we will focus on TDP-43 in ALS/FTLD, its nuclear and cytoplasmic functions, and consequences should these functions go awry.

Keywords

TDP-43 ALS FTLD RNA Granules 

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Marc Shenouda
    • 1
  • Ashley B. Zhang
    • 1
  • Anna Weichert
    • 1
  • Janice Robertson
    • 1
  1. 1.Tanz Centre for Research in Neurodegenerative Diseases and Department of Laboratory Medicine and PathobiologyUniversity of TorontoTorontoCanada

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