Mammalian Genome

, Volume 22, Issue 7–8, pp 420–448 | Cite as

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

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.

Notes

Acknowledgments

We thank Steve Thomas for graphics. The authors are supported by the Motor Neuron Disease Association, the UK Medical Research Council, and The Thierry Latran Foundation.

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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

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