RNA oxidation: A contributing factor or an epiphenomenon in the process of neurodegeneration

Abstract

In the past decade, RNA oxidation has caught the attention of many researchers, working to uncover its role in the pathogenesis of neurodegenerative diseases. It has been well documented that RNA oxidation is involved in a wide variety of neurological diseases and is an early event in the process of neurodegeneration. The analysis of oxidized RNA species revealed that at least messenger RNA (mRNA) and ribosomal RNA (rRNA) are damaged in several neurodegenerative diseases, including Alzheimer's disease and amyotrophic lateral sclerosis (ALS). The magnitude of the RNA oxidation, at least in mRNA, is significantly high at the early stage of the disease. Oxidative damage to mRNA is not random but selective and many oxidized mRNAs are related to the pathogenesis of the disease. Several studies have suggested that oxidative modification of RNA affects the translational process and consequently produces less protein and/or defective protein. Furthermore, several proteins have been identified to be involved in handling of damaged RNA. Although a growing body of studies suggests that oxidative damage to RNA may be associated with neuron deterioration, further investigation and solid evidence are needed. In addition, further uncovering of the consequences and cellular handling of the oxidatively damaged RNA should be important focuses in this area and may provide significant insights into the pathogenesis of neurodegenerative diseases.

Effects of axon degeneration on oligodendrocyte lineage cells: Dorsal rhizotomy evokes a repair response while axon degeneration rostral to spinal contusion induces both repair and apoptosis

“…In addition, nucleic acid oxidation has been suggested to be a potential factor in cell loss in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (Nunomura et al, 1999; Shan et al, 2003; Chang et al, 2008; Kong et al, 2008). We therefore examined nucleic acid oxidation as a marker for oxidative stress in both the rhizotomy and contusion models.…”

Oxidative damage to RNA but not DNA in the hippocampus of patients with major mental illness

“…26,27 Recent proteomic studies have identified many downregulated proteins in the postmortem brain tissue of patients with major depressive disorder, bipolar disorder and schizophrenia. [28][29][30][31] It will be interesting to determine whether RNA oxidative damage contributes to the downregulation of these proteins.…”

Biomarkers of Oxidative Stress in Blood

“…It is currently known that ribosomal and messenger RNA can be oxidized, and RNA-bound iron is also oxidized by the Fenton reaction (Honda et al 2005). Noncoding RNA species, such as transfer RNAs, microRNAs, and small nuclear and nucleolar RNAs, are also susceptible to oxidation (Kong et al 2008;Jacob et al 2013). The known molecular consequences of RNA oxidation are premature termination of reverse transcription, ribosomal dysfunction, aberrant and reduced protein synthesis, and translation of truncated or mutated proteins that are nonfunctional or prone to misfolding or aggregation (Rhee et al 1995;van Leeuwen et al 1998;Tanaka et al 2007;).…”