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Aging and disease    2019, Vol. 10 Issue (2) : 329-352     DOI: 10.14336/AD.2018.0409
Review |
MicroRNAs and the Genetic Nexus of Brain Aging, Neuroinflammation, Neurodegeneration, and Brain Trauma
Saumyendra N. Sarkar, Ashley E. Russell, Elizabeth B. Engler-Chiurazzi, Keyana N. Porter, James W. Simpkins*
Center for Basic and Translational Stroke Research, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV 26506, USA
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Abstract  

Aging is a complex and integrated gradual deterioration of cellular activities in specific organs of the body, which is associated with increased mortality. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, neurovascular disorders, and neurodegenerative diseases. There are nine tentative hallmarks of aging. In addition, several of these hallmarks are increasingly being associated with acute brain injury conditions. In this review, we consider the genes and their functional pathways involved in brain aging as a means of developing new strategies for therapies targeted to the neuropathological processes themselves, but also as targets for many age-related brain diseases. A single microRNA (miR), which is a short, non-coding RNA species, has the potential for targeting many genes simultaneously and, like practically all other cellular processes, genes associated with many features of brain aging and injury are regulated by miRs. We highlight how certain miRs can mediate deregulation of genes involved in neuroinflammation, acute neuronal injury and chronic neurodegenerative diseases. Finally, we review the recent progress in the development of effective strategies to block specific miR functions and discuss future approaches with the prediction that anti-miR drugs may soon be used in the clinic.

Keywords aging      microRNAs      brain      neuroinflammation      neurodegeneration      inflammaging     
Corresponding Authors: Simpkins James W.   
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These authors contributed equally to this study.

Issue Date: 10 February 2018
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Saumyendra N. Sarkar
Ashley E. Russell
Elizabeth B. Engler-Chiurazzi
Keyana N. Porter
James W. Simpkins
Cite this article:   
Saumyendra N. Sarkar,Ashley E. Russell,Elizabeth B. Engler-Chiurazzi, et al. MicroRNAs and the Genetic Nexus of Brain Aging, Neuroinflammation, Neurodegeneration, and Brain Trauma[J]. Aging and disease, 2019, 10(2): 329-352.
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http://www.aginganddisease.org/EN/10.14336/AD.2018.0409     OR     http://www.aginganddisease.org/EN/Y2019/V10/I2/329
Figure 1.  The hallmarks of mammalian aging and the miRs that target genetic networks involving these pathways. Associated miRs with each of the hallmark of aging are indicated. The miRs involving more than one aspect of aging are bolded.
Figure 2.  miR Biogenesis and Post-transcriptional Gene Regulation.
Figure 3.  MicroRNAs Target Enzyme-Scaffold Complex. Chains of molecules along with XRCC1 scaffolding protein recognize ROS induced DNA damage and recruit six enzymes to form the BER/SSBR-scaffold complex. MicroRNAs shown are identified by in silico analysis and target many components of this complex.
Figure 4.  miRs involved in deregulation of nutrient sensing pathway. Schematic diagram showing the growth hormone (GH) and insulin growth factor 1 (IGF-1) signaling pathway and its association with dietary restriction and aging. GH = Growth Hormone, PTEN = Phosphatase and Tensin homolog, PI3K = Phosphatidylinositol-4,5-bisphosphate 3-kinase, AKT = Protein kinase B, AMPK = AMP-activated protein kinase, Sirt1 = sirtuin (silent mating type information regulation 2 homolog) 1, mTOR = mechanistic target of rapamycin, PGC-1α = Peroxisome proliferator-activated receptor gamma coactivator 1-alpha, FOXO = FOXO family of Forkhead transcription factors.
Figure 5.  miRs specifically deregulate molecular chaperone specific pathway of proteostatis Oxidative and ER stress induced unfolded proteins either refolded back by HSP chaperone or degraded by HSC chaperone mediated ubiquitin-proteosome or lysomal pathways (Autophagy). Oxidative stress damages DNA and proteins leading to their reduced function. A miR-induced decrease in repair mechanisms would then encourage aging.
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