The role of transactive response DNA-binding protein-43 in amyotrophic lateral sclerosis and frontotemporal dementia

Ian R.A. Mackenzie, Rosa Rademakers

Research output: Contribution to journalReview article

49 Scopus citations

Abstract

Purpose of review: We examine current evidence that the transactive response DNA-binding protein (TDP-43) plays a pathogenic role in both amyotrophic lateral sclerosis and frontotemporal dementia. Recent findings: TDP-43 was recently identified as the major pathological protein in sporadic amyotrophic lateral sclerosis and in the most common pathological subtype of frontotemporal dementia, frontotemporal lobar degeneration with ubiquitinated inclusions. In these conditions, abnormal C-terminal fragments of TDP-43 are ubiquitinated, hyperphosphorylated and accumulate as cellular inclusions in neurons and glia. Cells with inclusions show absence of the normal nuclear TDP-43 localization. Recently, missense mutations in the gene encoding TDP-43 have been identified in patients with sporadic and familial amyotrophic lateral sclerosis. Summary: The recent discovery of pathological TDP-43 in both amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitinated inclusions confirms that these are closely related conditions within a new biochemical class of neurodegenerative disease, the TDP-43 proteinopathies.

Original languageEnglish (US)
Pages (from-to)693-700
Number of pages8
JournalCurrent opinion in neurology
Volume21
Issue number6
DOIs
StatePublished - Dec 1 2008

Keywords

  • Amyotrophic lateral sclerosis
  • Frontotemporal dementia
  • Frontotemporal lobar degeneration with ubiquitinated inclusions
  • Transactive response DNA-binding protein-43

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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