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RNA and Oxidative Stress in Alzheimer's Disease: Focus on microRNAs.
Oxid Med Cell Longev. 2020; 2020:2638130.OM

Abstract

Oxidative stress (OS) is one of the major pathomechanisms of Alzheimer's disease (AD), which is closely associated with other key events in neurodegeneration such as mitochondrial dysfunction, inflammation, metal dysregulation, and protein misfolding. Oxidized RNAs are identified in brains of AD patients at the prodromal stage. Indeed, oxidized mRNA, rRNA, and tRNA lead to retarded or aberrant protein synthesis. OS interferes with not only these translational machineries but also regulatory mechanisms of noncoding RNAs, especially microRNAs (miRNAs). MiRNAs can be oxidized, which causes misrecognizing target mRNAs. Moreover, OS affects the expression of multiple miRNAs, and conversely, miRNAs regulate many genes involved in the OS response. Intriguingly, several miRNAs embedded in upstream regulators or downstream targets of OS are involved also in neurodegenerative pathways in AD. Specifically, seven upregulated miRNAs (miR-125b, miR-146a, miR-200c, miR-26b, miR-30e, miR-34a, miR-34c) and three downregulated miRNAs (miR-107, miR-210, miR-485), all of which are associated with OS, are found in vulnerable brain regions of AD at the prodromal stage. Growing evidence suggests that altered miRNAs may serve as targets for developing diagnostic or therapeutic tools for early-stage AD. Focusing on a neuroprotective transcriptional repressor, REST, and the concept of hormesis that are relevant to the OS response may provide clues to help us understand the role of the miRNA system in cellular and organismal adaptive mechanisms to OS.

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Authors+Show Affiliations

Nunomura A
Department of Psychiatry, Jikei University School of Medicine, Tokyo, Japan.
Perry G
Department of Biology and Neurosciences Institute, University of Texas at San Antonio, San Antonio, USA.

MeSH

Alzheimer DiseaseAnimalsBrainDown-RegulationHumansMicroRNAsOxidation-ReductionOxidative StressUp-Regulation

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

33312335

Citation

Nunomura, Akihiko, and George Perry. "RNA and Oxidative Stress in Alzheimer's Disease: Focus On MicroRNAs." Oxidative Medicine and Cellular Longevity, vol. 2020, 2020, p. 2638130.
Nunomura A, Perry G. RNA and Oxidative Stress in Alzheimer's Disease: Focus on microRNAs. Oxid Med Cell Longev. 2020;2020:2638130.
Nunomura, A., & Perry, G. (2020). RNA and Oxidative Stress in Alzheimer's Disease: Focus on microRNAs. Oxidative Medicine and Cellular Longevity, 2020, 2638130. https://doi.org/10.1155/2020/2638130
Nunomura A, Perry G. RNA and Oxidative Stress in Alzheimer's Disease: Focus On MicroRNAs. Oxid Med Cell Longev. 2020;2020:2638130. PubMed PMID: 33312335.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - RNA and Oxidative Stress in Alzheimer's Disease: Focus on microRNAs. AU - Nunomura,Akihiko, AU - Perry,George, Y1 - 2020/11/30/ PY - 2020/07/23/received PY - 2020/10/21/revised PY - 2020/10/29/accepted PY - 2020/12/14/entrez PY - 2020/12/15/pubmed PY - 2021/9/8/medline SP - 2638130 EP - 2638130 JF - Oxidative medicine and cellular longevity JO - Oxid Med Cell Longev VL - 2020 N2 - Oxidative stress (OS) is one of the major pathomechanisms of Alzheimer's disease (AD), which is closely associated with other key events in neurodegeneration such as mitochondrial dysfunction, inflammation, metal dysregulation, and protein misfolding. Oxidized RNAs are identified in brains of AD patients at the prodromal stage. Indeed, oxidized mRNA, rRNA, and tRNA lead to retarded or aberrant protein synthesis. OS interferes with not only these translational machineries but also regulatory mechanisms of noncoding RNAs, especially microRNAs (miRNAs). MiRNAs can be oxidized, which causes misrecognizing target mRNAs. Moreover, OS affects the expression of multiple miRNAs, and conversely, miRNAs regulate many genes involved in the OS response. Intriguingly, several miRNAs embedded in upstream regulators or downstream targets of OS are involved also in neurodegenerative pathways in AD. Specifically, seven upregulated miRNAs (miR-125b, miR-146a, miR-200c, miR-26b, miR-30e, miR-34a, miR-34c) and three downregulated miRNAs (miR-107, miR-210, miR-485), all of which are associated with OS, are found in vulnerable brain regions of AD at the prodromal stage. Growing evidence suggests that altered miRNAs may serve as targets for developing diagnostic or therapeutic tools for early-stage AD. Focusing on a neuroprotective transcriptional repressor, REST, and the concept of hormesis that are relevant to the OS response may provide clues to help us understand the role of the miRNA system in cellular and organismal adaptive mechanisms to OS. SN - 1942-0994 UR - https://www.unboundmedicine.com/medline/citation/33312335/RNA_and_Oxidative_Stress_in_Alzheimer's_Disease:_Focus_on_microRNAs_ DB - PRIME DP - Unbound Medicine ER -