MicroRNAs in brain aging

Mohammed, Chand Parvez Danka; Park, Jun Soo; Nam, Hong Gil; Kim, Kee‐Tae

doi:10.1016/j.mad.2017.01.007

Cited by 57 publications

(34 citation statements)

References 60 publications

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“…MicroRNAs (miRNAs or miRs) are small noncoding RNAs (about 18-25 nucleotides in length) that regulate a vast array of physiological and pathological processes, ranging from development, homeostasis, metabolism and immunity, to aging and age-related diseases [102][103][104]. miRs bind mainly to the 3' untranslated region (UTR) of target mRNAs, and suppress their expression by inducing translational repression and/or degradation, depending on the complementarity Several studies revealed that the biogenesis of miRs could be self-regulated by cellular redox status, thus suggesting an additional intricate interplay between miRs production and ROS/ RNS levels [109].…”

Section: Oxidative Stress and Micrornasmentioning

confidence: 99%

Nrf2 Pathway in Age-Related Neurological Disorders: Insights into MicroRNAs

Paladino

Conte

Caggiano

et al. 2018

Cell Physiol Biochem

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A general hallmark of neurological diseases is the loss of redox homeostasis that triggers oxidative damages to biomolecules compromising neuronal function. Under physiological conditions the steady-state concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are finely regulated for proper cellular functions. Reduced surveillance of endogenous antioxidant defenses and/or increased ROS/RNS production leads to oxidative stress with consequent alteration of physiological processes. Neuronal cells are particularly susceptible to ROS/RNS due to their biochemical composition. Overwhelming evidences indicate that nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-linked pathways are involved in protective mechanisms against oxidative stress by regulating antioxidant and phase II detoxifying genes. As such, Nrf2 deregulation has been linked to both aging and pathogenesis of many human chronic diseases, including neurodegenerative ones such as Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis. Nrf2 activity is tightly regulated by a fine balance between positive and negative modulators. A better understanding of the regulatory mechanisms underlying Nrf2 activity could help to develop novel therapeutic interventions to prevent, slow down or possibly reverse various pathological states. To this end, microRNAs (miRs) are attractive candidates because they are linked to intracellular redox status being regulated and, post-transcriptionally, regulating key components of ROS/RNS pathways, including Nrf2.

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Section: Oxidative Stress and Micrornasmentioning

confidence: 99%

Nrf2 Pathway in Age-Related Neurological Disorders: Insights into MicroRNAs

Paladino

Conte

Caggiano

et al. 2018

Cell Physiol Biochem

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“…It is possible that the microglia response is molecularly preprogrammed prior to exposure to exogenous insult, and that this programming changes with aging. Aging is known to greatly influence gene expression in the brain (Kang et al, 2011 ), and such changes in gene expression are tightly regulated by epigenetic modifications, including DNA methylation (DNAm; Zampieri et al, 2015 ), histone modifications (Gong et al, 2015 ), and micro RNAs (Danka Mohammed et al, 2017 ). Indeed, DNAm pattens in brain have been shown to change dynamically throughout the human lifespan (Numata et al, 2012 ), and epigenetic processes involved in aging have been well studied (Day et al, 2013 ; Sen et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Epigenetics of Delirium and Aging: Potential Role of DNA Methylation Change on Cytokine Genes in Glia and Blood Along With Aging

Shinozaki

Braun

Hing

et al. 2018

Front. Aging Neurosci.

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Background: Delirium in elderly patients is common and dangerous. Major risk factors include aging and exogenous insults, such as infection or surgery. In animal models, aging enhances pro-inflammatory cytokine release from microglia in response to exogenous insults. The epigenetic mechanism DNA methylation (DNAm) regulates gene expression and changes with age. Older individuals may have methylation changes that influence the increased cytokine upon insult, but the degree to which aging affects DNAm of cytokine genes is not fully understood.Methods: The relationship between DNAm and aging of pro-inflammatory cytokine genes (TNF-alpha, IL1-beta, IL-6) was investigated using methylation array data in two cohorts. Brain and blood samples were collected from a neurosurgery cohort (NSG) of 21 subjects who underwent brain resection. A second cohort, the Grady Trauma Project (GTP), included blood samples from 265 subjects.Results: In the NSG cohort, a significant negative correlation between age and DNAm in brain was found at a CpG in IL-6. With the GTP dataset, significant negative correlations between age and DNAm were seen at most of the CpGs in TNF-alpha. Also, TNF-Alpha expression increases with age. These GTP DNAm correlations were also nominally significant in NSG blood samples. In neuronal negative NSG brain tissue, a similar negative trend was observed.Conclusions: With aging, a decrease in DNAm of cytokines gene CpGs in glia and blood was seen. As this can affect their expression, additional research is needed to fully elucidate the role of DNAm in aging and how it may influence the pathogenesis of delirium.

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“…Several miRNAs have been shown to play signi cant role in brain and neuronal development 19 . Aberrant expression of miRNAs may predict onset of cognitive dysfunctions 20 . Recently, the role of altered miRNAs in the diagnosis for AD has been extensively studied.…”

Section: Read Full Licensementioning

confidence: 99%

Plasma miRNAs as Biomarkers for Amnestic Mild Cognitive Impairment and Modulation on BACE1

Yang

Zhang

et al. 2020

Preprint

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Background: Amnestic mild cognitive impairment (aMCI) is a prodromal stage of Alzheimer’s disease with the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) imbalance. Altered microRNAs (miRNA) associated with BACE1 may be potential biomarkers for aMCI diagnosis. The aims of this study were to find an effective diagnostic model for aMCI, and to explore the modulation of candidate miRNAs on BACE1 expression.Methods: Plasma RNA was extracted from participants enrolled in China longitudinal aging study (CLAS). MiRNA profiling was performed using microarray sequencing on a discovery set, compromising five aMCI subjects that confirmed by 18F-Flutemetamol PET scan and five normal controls (NC). Quantitative reverse transcription PCR was used to validate the expression levels of differently expressed miRNAs on an analysis set (20 aMCI subjects and 10 NC). Diagnostic capability of candidate miRNAs was assessed in a validation set (40 aMCI subjects and 40 NC). Modulation of candidate miRNAs on BACE1 was explored in rat and human hippocampal neurons in vitro through transfection of miRNA mimics or inhibitor lentivirus.Results: In discovery set, we verified 46 significantly differentially expressed miRNAs between aMCI and NC groups (P<0.05). Among these, 33 miRNAs were down-regulated and 13 miRNAs were up-regulated. In analysis set, miR-1185-2-3p, miR-1909-3p, miR-22-5p, and miR-134-3p also significantly decreased in aMCI group. Four miRNAs above and miR-107 which was found to decline in previous study were selected as potential biomarkers. A diagnostic model consists of five miRNAs above had an outstanding diagnostic accuracy (81.25%) to diagnose aMCI. Except for miR-134-3p, other four miRNAs modulated BACE1 expression and C-terminal fragments-beta production effectively in rat hippocampal neurons in vitro. Similar modulation of miR-1185-2-3p and miR-1909-3p were confirmed in human hippocampal neurons in vitro.Conclusion: A diagnostic model consists of five plasma miRNAs could be novel biomarker for aMCI diagnosis. These miRNAs might be involved in pathogenesis of AD through regulating expression of BACE1.

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MicroRNAs in brain aging

Cited by 57 publications

References 60 publications

Nrf2 Pathway in Age-Related Neurological Disorders: Insights into MicroRNAs

Nrf2 Pathway in Age-Related Neurological Disorders: Insights into MicroRNAs

Epigenetics of Delirium and Aging: Potential Role of DNA Methylation Change on Cytokine Genes in Glia and Blood Along With Aging

Plasma miRNAs as Biomarkers for Amnestic Mild Cognitive Impairment and Modulation on BACE1

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