TDP-43 Epigenetic Facets and Their Neurodegenerative Implications

Juliette Gimenez, Alida Spalloni, Sara Cappelli, Francesca Ciaiola, Valerio Orlando, Emanuele Buratti, Patrizia Longone

Research output: Contribution to journalArticlepeer-review


Since its initial involvement in numerous neurodegenerative pathologies in 2006, either as a principal actor or as a cofactor, new pathologies implicating transactive response (TAR) DNA-binding protein 43 (TDP-43) are regularly emerging also beyond the neuronal system. This reflects the fact that TDP-43 functions are particularly complex and broad in a great variety of human cells. In neurodegenerative diseases, this protein is often pathologically delocalized to the cytoplasm, where it irreversibly aggregates and is subjected to various post-translational modifications such as phosphorylation, polyubiquitination, and cleavage. Until a few years ago, the research emphasis has been focused particularly on the impacts of this aggregation and/or on its widely described role in complex RNA splicing, whether related to loss- or gain-of-function mechanisms. Interestingly, recent studies have strengthened the knowledge of TDP-43 activity at the chromatin level and its implication in the regulation of DNA transcription and stability. These discoveries have highlighted new features regarding its own transcriptional regulation and suggested additional mechanistic and disease models for the effects of TPD-43. In this review, we aim to give a comprehensive view of the potential epigenetic (de)regulations driven by (and driving) this multitask DNA/RNA-binding protein.
Original languageEnglish (US)
Pages (from-to)13807
JournalInternational journal of molecular sciences
Issue number18
StatePublished - Sep 7 2023

Bibliographical note

KAUST Repository Item: Exported on 2023-09-11
Acknowledgements: Funding was provided by the Fondazione Italiana AriSLA call 2018, Project “PathensTDP”, and the JPND European program call 2020, Project “ImageTDP43“ (Reference Number: JPND2020-568-078).

ASJC Scopus subject areas

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


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