title: SOD1 and TDP-43 animal models of amyotrophic lateral sclerosis: recent advances in understanding disease toward the development of clinical treatments.
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.
authors.affiliation: MRC Mammalian Genetics Unit, Harwell, Oxfordshire, UK. p.joyce@har.mrc.ac.uk
authors.forename: Peter I
authors.initials: PI
authors.lastname: Joyce
authors.forename: Pietro
authors.initials: P
authors.lastname: Fratta
authors.forename: Elizabeth M C
authors.initials: EM
authors.lastname: Fisher
authors.forename: Abraham
authors.initials: A
authors.lastname: Acevedo-Arozena
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D017173:Caenorhabditis elegans; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D004330:Drosophila; D006801:Humans; D051379:Mice; D051381:Rats; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D015027:Zebrafish
chemical_list: D004268:DNA-Binding Proteins; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1