Sublethal RNA Oxidation as a Mechanism for Neurodegenerative Disease

International Journal of Molecular Sciences

Rudy J. Castellani³  Akihiko Nunomura⁴  Raj K. Rolston¹  Paula I. Moreira⁵  Atsushi Takeda²  George Perry¹ 

[1]Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA

[2]Department of Neurology, Tohoku University School of Medicine, Sendai, Japan

[3]Department of Pathology, University of Maryland, Baltimore, Maryland, USA

[4]Department of Neuropsychiatry, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan

[5]Center for Neuroscience and Cell Biology of Coimbra, University of Coimbra, Coimbra, Portugal

关键词: Alzheimer disease;    8-oxoguanosine;    neurodegeneration;    oxidative damage;    Parkinson disease;    RNA;   

DOI  :  10.3390/ijms9050789

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2008 by MDPI