Mammalian Genome

, Volume 22, Issue 7, pp 420–448

SOD1 and TDP-43 animal models of amyotrophic lateral sclerosis: recent advances in understanding disease toward the development of clinical treatments

  • Peter I. Joyce
  • Pietro Fratta
  • Elizabeth M. C. Fisher
  • Abraham Acevedo-Arozena
Article

DOI: 10.1007/s00335-011-9339-1

Cite this article as:
Joyce, P.I., Fratta, P., Fisher, E.M.C. et al. Mamm Genome (2011) 22: 420. doi:10.1007/s00335-011-9339-1

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease with no cure. Breakthroughs in understanding ALS pathogenesis came with the discovery of dominant mutations in the superoxide dismutase 1 gene (SOD1) and other genes, including the gene encoding transactivating response element DNA binding protein-43 (TDP-43). This has led to the creation of animal models to further our understanding of the disease and identify a number of ALS-causing mechanisms, including mitochondrial dysfunction, protein misfolding and aggregation, oxidative damage, neuronal excitotoxicity, non-cell autonomous effects and neuroinflammation, axonal transport defects, neurotrophin depletion, effects from extracellular mutant SOD1, and aberrant RNA processing. Here we summarise the SOD1 and TDP-43 animal models created to date, report on recent findings supporting the potential mechanisms of ALS pathogenesis, and correlate this understanding with current developments in the clinic.

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Peter I. Joyce
    • 1
  • Pietro Fratta
    • 2
  • Elizabeth M. C. Fisher
    • 2
  • Abraham Acevedo-Arozena
    • 1
  1. 1.MRC Mammalian Genetics UnitHarwellUK
  2. 2.UCL Institute of NeurologyLondonUK