Sublethal RNA oxidation as a mechanism for neurodegenerative disease

Rudy J. Castellani, Akihiko Nunomura, Raj K. Rolston, Paula I. Moreira, Atsushi Takeda, George Perry, Mark A. Smith

Research output: Contribution to journalReview article

30 Citations (Scopus)

Abstract

Although cellular RNA is subjected to the same oxidative insults as DNA and other cellular macromolecules, oxidative damage to RNA has not been a major focus in investigations of the biological consequences of free radical damage. In fact, because it is largely single-stranded and its bases lack the protection of hydrogen bonding and binding by specific proteins, RNA may be more susceptible to oxidative insults than is DNA. Oxidative damage to protein-coding RNA or non-coding RNA will, in turn, potentially cause errors in proteins and/or dysregulation of gene expression. While less lethal than mutations in the genome, such sublethal insults to cells might be associated with underlying mechanisms of several chronic diseases, including neurodegenerative disease. Recently, oxidative RNA damage has been described in several neurodegenerative diseases including Alzheimer disease, Parkinson disease, dementia with Lewy bodies, and prion diseases. Of particular interest, oxidative RNA damage can be demonstrated in vulnerable neurons early in disease, suggesting that RNA oxidation may actively contribute to the onset of the disease. An increasing body of evidence suggests that, mechanistically speaking, the detrimental effects of oxidative RNA damage to protein synthesis are attenuated, at least in part, by the existence of protective mechanisms that prevent the incorporation of the damaged ribonucleotides into the translational machinery. Further investigations aimed at understanding the processing mechanisms related to oxidative RNA damage and its consequences may provide significant insights into the pathogenesis of neurodegenerative and other degenerative diseases and lead to better therapeutic strategies.

Original languageEnglish
Pages (from-to)789-806
Number of pages18
JournalInternational journal of molecular sciences
Volume9
Issue number5
DOIs
Publication statusPublished - 2008 May

Keywords

  • 8-oxoguanosine
  • Alzheimer disease
  • Neurodegeneration
  • Oxidative damage
  • Parkinson disease
  • RNA

ASJC Scopus subject areas

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

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  • Cite this

    Castellani, R. J., Nunomura, A., Rolston, R. K., Moreira, P. I., Takeda, A., Perry, G., & Smith, M. A. (2008). Sublethal RNA oxidation as a mechanism for neurodegenerative disease. International journal of molecular sciences, 9(5), 789-806. https://doi.org/10.3390/ijms9050789