Tdp-43 and inflammation: implications for amyotrophic lateral sclerosis and frontotemporal dementia

Fiona Bright, Gabriella Chan, Annika van Hummel, Lars M. Ittner, Yazi D. Ke

Research output: Contribution to journalReview articlepeer-review

22 Citations (Scopus)


The abnormal mislocalisation and ubiquitinated protein aggregation of the TAR DNA binding protein 43 (TDP-43) within the cytoplasm of neurons and glia in the central nervous system (CNS) is a pathological hallmark of early-onset neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The pathomechanisms underlying abnormal mislocalisation and aggregation of TDP-43 remain unknown. However, there is a growing body of evidence implicating neuroinflammation and immune-mediated mechanisms in the pathogenesis of neurodegeneration. Importantly, most of the evidence for an active role of immunity and inflammation in the pathogenesis of ALS and FTD relates specifically to TDP-43, posing the question as to whether immune-mediated mechanisms could hold the key to understanding TDP-43’s underlying role in neurodegeneration in both diseases. Therefore, this review aims to piece together key lines of evidence for the specific association of TDP-43 with key immune and inflammatory pathways to explore the nature of this relationship and the implications for potential pathomechanisms underlying neurodegeneration in ALS and FTD.

Original languageEnglish
Article number7781
JournalInternational Journal of Molecular Sciences
Issue number15
Publication statusPublished or Issued - 1 Aug 2021
Externally publishedYes


  • ALS
  • FTD
  • Immunity
  • Neurodegeneration
  • Neuroinflammation
  • TDP-43

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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