Messenger RNA oxidation occurs early in disease pathogenesis and promotes motor neuron degeneration in ALS.

Abstract

BACKGROUND:

Accumulating evidence indicates that RNA oxidation is involved in a wide variety of neurological diseases and may be associated with neuronal deterioration during the process of neurodegeneration. However, previous studies were done in postmortem tissues or cultured neurons. Here, we used transgenic mice to demonstrate the role of RNA oxidation in the process of neurodegeneration.

METHODOLOGY/PRINCIPAL FINDINGS:

We demonstrated that messenger RNA (mRNA) oxidation is a common feature in amyotrophic lateral sclerosis (ALS) patients as well as in many different transgenic mice expressing familial ALS-linked mutant copper-zinc superoxide dismutase (SOD1). In mutant SOD1 mice, increased mRNA oxidation primarily occurs in the motor neurons and oligodendrocytes of the spinal cord at an early, pre-symptomatic stage. Identification of oxidized mRNA species revealed that some species are more vulnerable to oxidative damage, and importantly, many oxidized mRNA species have been implicated in the pathogenesis of ALS. Oxidative modification of mRNA causes reduced protein expression. Reduced mRNA oxidation by vitamin E restores protein expression and partially protects motor neurons.

CONCLUSION/SIGNIFICANCE:

These findings suggest that mRNA oxidation is an early event associated with motor neuron deterioration in ALS, and may be also a common early event preceding neuron degeneration in other neurological diseases.

• Authors: Yueming Chang, Qiongman Kong, Xiu Shan, Guilian Tian, Hristelina Ilieva, Don W Cleveland, Jeffrey D Rothstein, David R Borchelt, Philip C Wong, Chien-Liang Glenn Lin
• Journal: PloS one (PLoS One) Vol. 3 Issue 8 Pg. e2849 (Aug 06 2008) ISSN: 1932-6203 [Electronic] United States
• PMID: 18682740 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• SOD1 protein, human
• Sod1 protein, mouse
• Superoxide Dismutase
• Superoxide Dismutase-1

Topics

• Animals
• Humans
• Mice
• Mice, Mutant Strains
• Motor Cortex (metabolism)
• Motor Neuron Disease (genetics, metabolism)
• Nerve Degeneration
• Oxidation-Reduction
• RNA, Messenger (genetics, metabolism)
• Spinal Cord (metabolism)
• Superoxide Dismutase (genetics, metabolism)
• Superoxide Dismutase-1