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

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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.

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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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  1. MRC Mammalian Genetics Unit, Harwell, Oxfordshire, OX11 0RD, UK

    Peter I. Joyce & Abraham Acevedo-Arozena

  2. UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK

    Pietro Fratta & Elizabeth M. C. Fisher

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  1. Peter I. Joyce
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  2. Pietro Fratta
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  4. Abraham Acevedo-Arozena
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Correspondence to Peter I. Joyce.

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Joyce, P.I., Fratta, P., Fisher, E.M.C. et al. SOD1 and TDP-43 animal models of amyotrophic lateral sclerosis: recent advances in understanding disease toward the development of clinical treatments. Mamm Genome 22, 420–448 (2011). https://doi.org/10.1007/s00335-011-9339-1

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