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Role of Oxidative RNA Damage in Aging and Neurodegenerative Disorders Akihiko Nunomura 1 1Department of Neuropsychiatry, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi Keyword: aging , 8-hydroxyguanosine , neurodegeneration , oxidative stress , RNA pp.179-194
Published Date 2013/2/1
DOI https://doi.org/10.11477/mf.1416101418
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Abstract

 It is now clear that RNA species not only encode proteins but also fulfill critical roles in regulating gene expression. Compared to other species, humans probably contain more non-coding RNAs, especially in the brain, where the non-coding RNAs may play a significant role in cognition. In neurons of human and rodent brains, oxidative damage to nucleic acids, predominantly to RNA, increases as a function of age; this may play a crucial role in the development of age-associated neurodegeneration. Indeed, compared to age-matched controls, patients with neurodegenerative disorders, including Alzheimer disease, Parkinson disease, dementia with Lewy bodies, and amyotrophic lateral sclerosis, show higher levels of neuronal RNA oxidation. Furthermore, oxidative damage to RNA has been found in cellular and animal models of neurodegeneration. RNA oxidation has been hypothesized to cause aberrant expression of microRNAs and proteins and subsequently initiate inappropriate cell fate pathways. Interestingly, accumulating evidence obtained from studies on either human samples or experimental models coincidentally suggests that RNA oxidation is a feature of neurons in the aging brain and more prominently observed in vulnerable neurons at an early-stage of age-associated neurodegenerative disorders, indicating that RNA oxidation actively contributes to the prodromal stage, onset, and development of these disorders. 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 disorders and pave the way for novel therapeutic strategies.


Copyright © 2013, Igaku-Shoin Ltd. All rights reserved.

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電子版ISSN 1344-8129 印刷版ISSN 1881-6096 医学書院

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