Topoisomerase-Mediated DNA Damage in Neurological Disorders

Morgan Crewe, Ram Madabhushi

Research output: Contribution to journalReview articlepeer-review

6 Scopus citations


The nervous system is vulnerable to genomic instability and mutations in DNA damage response factors lead to numerous developmental and progressive neurological disorders. Despite this, the sources and mechanisms of DNA damage that are most relevant to the development of neuronal dysfunction are poorly understood. The identification of primarily neurological abnormalities in patients with mutations in TDP1 and TDP2 suggest that topoisomerase-mediated DNA damage could be an important underlying source of neuronal dysfunction. Here we review the potential sources of topoisomerase-induced DNA damage in neurons, describe the cellular mechanisms that have evolved to repair such damage, and discuss the importance of these repair mechanisms for preventing neurological disorders.

Original languageEnglish (US)
Article number751742
JournalFrontiers in Aging Neuroscience
StatePublished - Nov 25 2021


  • DNA cleavage complexes
  • TDP1
  • TDP2
  • neurodegeneration
  • topoisomerase

ASJC Scopus subject areas

  • Aging
  • Cognitive Neuroscience


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