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The Journal of Neuroscience, June 15, 2003, 23(12):4913-4921

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The Identification and Characterization of Oxidized RNAs in Alzheimer's Disease

Xiu Shan,^1,2 Hirofumi Tashiro,¹ and Chien-liang Glenn Lin^1,2,3,4

¹Department of Neuroscience, ²Neuroscience Graduate Studies Program, and ³Ohio State Biochemistry Program and ⁴Integrated Biomedical Sciences Graduate Program, The Ohio State University, Columbus, Ohio 43210

It has been shown that cytoplasmic RNA oxidation occurs to a great extent in the brains of Alzheimer's disease (AD) patients. The goal of this study was to isolate and identify oxidized RNA species in AD. We show that significant amounts of poly(A)⁺ mRNAs are oxidized in AD brains. RNA oxidation is not random but highly selective. Importantly, many identified oxidized mRNA species have been implicated in the pathogenesis of AD. Quantitative analysis revealed that some mRNA species are more susceptible to oxidative damage. We also investigated the biological consequence of oxidatively damaged mRNAs by expressing them in cell lines. Our data indicated that abnormal processing of proteins occurred to the oxidized mRNAs. This may implicate the potential contribution of RNA oxidation in the pathogenesis of AD.

Key words: Alzheimer's disease; oxidative damage; 8-oxo-7,8-dihydroguanosine; 8OHG; RNA oxidation; reactive oxygen species; protein aggregation

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Received Jan. 16, 2003; revised Mar. 28, 2003; accepted Apr. 2, 2003.

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