Oxidative damage to RNA in aging and neurodegenerative disorders

Akihiko Nunomura*, Paula I. Moreira, Rudy J. Castellani, Hyoung Gon Lee, Xiongwei Zhu, Mark A. Smith, George Perry

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

124 Scopus citations

Abstract

An age-associated increase in oxidative damage to nucleic acids, predominantly to RNA, has been recently demonstrated in neurons of human and rodent brains, which may play a fundamental role in the development of age-associated neurodegeneration. Indeed, more prominent levels of neuronal RNA oxidation compared to normal aging have been described in neurodegenerative disorders including Alzheimer disease, Parkinson disease, dementia with Lewy bodies, and amyotrophic lateral sclerosis. Moreover, oxidative damage to RNA has been found also in cellular and animal model of neurodegeneration. Oxidative RNA modification can occur not only in protein-coding RNAs but also in non-coding RNAs that are recently revealed to contribute towards the complexity of the mammalian brain. It has been hypothesized that RNA oxidation causes aberrant expression of microRNAs and proteins and subsequently initiates inappropriate cell fate pathways. While less lethal than mutations in the genome and not inheritable, such sublethal damage to cells might be associated with underlying mechanisms of degeneration, especially age-associated neurodegeneration. Of particular interest, the accumulating evidence obtained from studies on either human samples or experimental models coincidentally suggests that RNA oxidation is a feature in neurons of aging brain and more prominently observed in vulnerable neurons at early-stage of age-associated neurodegenerative disorders, indicating that RNA oxidation actively contributes to the background, the onset, and the development of the disorders. Further investigations aimed at understanding of the processing mechanisms related to oxidative RNA damage and its consequences may provide significant insights into the pathogenesis of neurodegenerative disorders and lead to better therapeutic strategies.

Original languageEnglish (US)
Pages (from-to)231-248
Number of pages18
JournalNeurotoxicity Research
Volume22
Issue number3
DOIs
StatePublished - Oct 2012
Externally publishedYes

Keywords

  • 8-Hydroxyguanosine
  • Aging
  • Neurodegeneration
  • Nucleic acids
  • Oxidative stress
  • RNA

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

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