RNA Oxidation in Neurodegenerative Diseases: Sublethal Damage as a Mechanism for Chronic Degeneration

Because RNA is largely single-stranded and its bases are not protected by hydrogen bonding and less protected by specific proteins, RNA may be more susceptible to oxidative insults than DNA. This is a reasonable proposition given also that cellular RNA locates in the vicinity of mitochondria, the primary source of reactive oxygen species. Although the biological consequences of oxidative RNA damage have not been fully understood yet, oxidative damage to protein-coding RNA and non-coding RNA will potentially cause errors in proteins and dysregulation of gene expression. While less lethal than mutations in genome, such sublethal damage to cells might be associated with underlying mechanisms of chronic degeneration. Recently, oxidative RNA damage has been described in most of the common neurodegenerative diseases including Alzheimer disease, Parkinson disease, dementia with Lewy bodies, and amyotrophic lateral sclerosis. Of particular interest, oxidative RNA damage is a feature in vulnerable neurons at early-stage of these diseases, suggesting that RNA oxidation actively contributes to the onset or the development of the diseases. 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 diseases and lead to better therapeutic strategies.