Gains or losses: molecular mechanisms of TDP43-mediated neurodegeneration

Nat Rev Neurosci. 2011 Nov 30;13(1):38-50. doi: 10.1038/nrn3121.


RNA-binding proteins, and in particular TAR DNA-binding protein 43 (TDP43), are central to the pathogenesis of motor neuron diseases and related neurodegenerative disorders. Studies on human tissue have implicated several possible mechanisms of disease and experimental studies are now attempting to determine whether TDP43-mediated neurodegeneration results from a gain or a loss of function of the protein. In addition, the distinct possibility of pleotropic or combined effects - in which gains of toxic properties and losses of normal TDP43 functions act together - needs to be considered.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Genetic Predisposition to Disease*
  • Humans
  • Models, Biological
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology
  • Phosphorylation / genetics
  • Protein Processing, Post-Translational / physiology
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Ubiquitination / physiology


  • DNA-Binding Proteins
  • RNA-Binding Proteins