RNA Oxidation in Alzheimer and Parkinson Diseases

Summary: RNA is oxidised in some of Alzheimer's, Parkinson's and Down syndrome patients' neurons

Interestingness: 2

Paper by Akihiko Nunomura, George Perry, Jing Zhang, Thomas J Montine, Atsushi Takeda, Shigeru Chiba and Mark A Smith in the Journal of Anti-Aging Medicine, Volume 2, Issue 3, Fall 1999.

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They measured 8-hydroxydeoxyguanosine (8-OHdG) and 8-hydroxyguanosine (8-OHG) as markers for DNA and RNA oxidation respectively in an unknown number of brains of postmortem Alzheimer's (AD), Parkinson's (PD) and Down syndrome (DS) patients. They found more 8-OHG in some parts of the brains of some types of disease, and less in others, but the parts of the brain still don't mean much to me. In any case, here they are:

• More oxidation in the cytoplasm than in the nucleolus and nuclear envelope in the neurons of AD and DS, clean in controls
• No difference in cerebellum between AD, DS and controls
• RNA oxidation was the main thing being detected in AD and DS
• Less oxidation with increased amyloid beta (AB) and neurofibrillary tangles (NFT)
• Increased oxidation in substantia negra in PD, dementia with Lewy bodies (DLB), and multiple system atrophy-Parkinsonian type (MSA-P). More in PD than other two
• Both RNA and DNA oxidation in PD, DLB and MSA-P
• No increase in RNA oxidation in PD in cerebellum or cerebral cortex, but increase in cerebral cortex for DLB

They think the source of oxidation is damaged mitochondria spewing hydrogen peroxide, and it transforming to hydroxyl radicals through the Fenton reaction in the cytoplasm. They don't know what effect oxidation has on RNA's functionality or if it is important. Probably some translation issues with wrong base pairing.
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Abstract follows:

In Alzheimer and Parkinson diseases, oxidative alterations, affecting lipids, proteins, and DNA, have been described. Using an in situ approach to identify 8-hydroxyguanosine, an oxidized nucleoside, we recently identified RNA as a major target of oxidation in Alzheimer and Parkinson diseases as well as Down syndrome, where premature Alzheimer-like neuropathology is invariably found. RNA oxidation is localized to the neuronal populations potentially affected in these diseases. Together with the known mitochondrial dysfunction in Alzheimer and Parkinson diseases, the cytoplasmic predominance of neuronal 8-hydroxyguanosine supports mitochondria as the most likely source of reactive oxygen responsible for RNA oxidation. The consequence of oxidatively damaged RNA is not fully understood; however, the potential of oxidized RNA to cause errors in translation indicates a metabolic abnormality in neurodegenerative diseases.