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RNA oxidation in Alzheimer disease and related neurodegenerative disorders

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Abstract

RNA oxidation and its biological effects are less well studied compared to DNA oxidation. However, RNA may be more susceptible to oxidative insults than DNA, for RNA is largely single-stranded and its bases are not protected by hydrogen bonding and less protected by specific proteins. Also, cellular RNA locates in the vicinity of mitochondria, the primary source of reactive oxygen species. Oxidative modification can occur not only in protein-coding RNAs, but also in non-coding RNAs that have been recently revealed to contribute towards the complexity of the mammalian brain. Damage to coding and non-coding RNAs will cause errors in proteins and disturbances in the regulation of gene expression. 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 that is commonly found in the elderly population. Indeed, oxidative RNA damage has been described recently in most of the common neurodegenerative disorders including Alzheimer disease, Parkinson disease, dementia with Lewy bodies and amyotrophic lateral sclerosis. Of particular interest, the accumulating evidence obtained from studies on either human samples or experimental models coincidentally suggests that oxidative RNA damage is a feature in vulnerable neurons at early-stage of these neurodegenerative disorders, indicating that RNA oxidation actively contributes to the onset or 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.

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Authors and Affiliations

  1. Department of Neuropsychiatry, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan

    Akihiko Nunomura

  2. Division of Clinical Research, Department of Aging and Geriatrics, and Genomics and Biomarkers Core of the Institute on Aging, University of Florida, Gainesville, FL, 32611, USA

    Tim Hofer

  3. Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

    Paula I. Moreira

  4. Department of Pathology, University of Maryland, Baltimore, MD, USA

    Rudy J. Castellani

  5. Department of Pathology, Case Western Reserve University, Cleveland, OH, 44106, USA

    Mark A. Smith & George Perry

  6. College of Sciences, University of Texas at San Antonio, 6900 North Loop 1604 West, San Antonio, TX, 78249-0661, USA

    George Perry

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  1. Akihiko Nunomura
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  2. Tim Hofer
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  3. Paula I. Moreira
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  4. Rudy J. Castellani
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  5. Mark A. Smith
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  6. George Perry
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Correspondence to Akihiko Nunomura or George Perry.

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Nunomura, A., Hofer, T., Moreira, P.I. et al. RNA oxidation in Alzheimer disease and related neurodegenerative disorders. Acta Neuropathol 118, 151–166 (2009). https://doi.org/10.1007/s00401-009-0508-1

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  • DOI: https://doi.org/10.1007/s00401-009-0508-1

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