TDP-43-based animal models of neurodegeneration: new insights into ALS pathology and pathophysiology

Neurodegener Dis. 2011;8(4):262-74. doi: 10.1159/000321547. Epub 2010 Dec 3.


The clinical and pathological overlap between amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) suggests these diseases share common underlying mechanisms, a suggestion underscored by the discovery that TDP-43 inclusions are a key pathologic feature in both ALS and FTLD. This finding, combined with the identification of TDP-43 mutations in ALS, directly implicates this DNA/RNA binding protein in disease pathogenesis in ALS and FTLD. However, many key questions remain, including what is the normal function of TDP-43, and whether disease-associated mutations produce toxicity in the nucleus, cytoplasm or both. Furthermore, although pathologic TDP-43 inclusions are clearly associated with many forms of neurodegeneration, whether TDP-43 aggregation is a key step in the pathogenesis in ALS, FTLD and other disorders remains to be proven. This review will compare the features of numerous recently developed animal models of TDP-43-related neurodegeneration, and discuss how they contribute to our understanding of the pathogenesis of human ALS and FTLD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / physiopathology*
  • Animals
  • DNA-Binding Proteins / genetics*
  • Disease Models, Animal
  • Frontotemporal Lobar Degeneration / genetics
  • Frontotemporal Lobar Degeneration / physiopathology
  • Humans
  • Nerve Degeneration / genetics
  • Nerve Degeneration / physiopathology


  • DNA-Binding Proteins