TDP-43 proteinopathy

TDP-43 proteinopathies are a set of neurodegenerative disorders characterized pathologically by cytoplasmic inclusions composed of TDP-43. The pathology has been implicated in three major diseases:

Others neurodegenerative disorders are less well known to feature TDP-43 proteinopathy 1,4,5:


TDP-43 is the abbreviation for transactive response (TAR) DNA-binding protein of 43 kDa, which is encoded by the TARDBP gene. The protein binds to nucleic acids and some proteins, serving multiple functions in the regulation of gene expression at the transcription and translation levels. It is expressed in nearly all tissues normally. In disease states, the protein is hyperphosphorylated, ubiquitinated, and cleaved to generate C-terminus fragments 2,4. Cells in affected central nervous system regions stain with antibodies against phosphorylated TDP-43, demonstrating aggregates of protein mislocalized to the cytoplasm 3,4.

Neurodegenerative diseases

Neurodegenerative diseases are legion and their classification just as protean. A useful approach is to divide them according to underlying pathological process, although even using this schema, there is much overlap and thus resulting confusion.

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Article information

rID: 70411
Section: Pathology
Synonyms or Alternate Spellings:
  • TDP-43 proteinopathies
  • TDP-43-related neurodegeneration
  • TAR DNA-binding protein 43 proteinopathy
  • TAR DNA-binding protein of 43 kDa proteinopathy

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Cases and figures

  • Figure 1: FTLD phenotypic overlap
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