MicroRNA-132 provides neuroprotection for tauopathies via multiple signaling pathways

Fatimy, Rachid El; Li, Shaomin; Chen, Zhicheng; Mushannen, Tasnim; Gongala, Sree; Wei, Zhiyun; Balu, Darrick T.; Rabinovsky, Rosalia; Cantlon, Adam; Elkhal, Abdallah; Selkoe, Dennis J.; Sonntag, Kai‐Christian; Walsh, Dominic M.; Krichevsky, Anna M.

doi:10.1007/s00401-018-1880-5

Cited by 110 publications

(107 citation statements)

References 71 publications

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“…MiRNA‐219 is reduced in AD brain and regulates tau in vivo . MiRNA‐132 is able to protect against tauopathies . We demonstrated that in hippocampus, miRNA‐219 and miRNA‐15a were reduced post dAGEs intervention, while quercetin is able to elevate miRNA‐219 and miRNA‐15a, in addition, quercetin also elevated miRNA‐132.…”

Section: Discussionmentioning

confidence: 73%

DietaryAdvancedGlycationEnd Products–InducedCognitive Impairment in Aged ICR Mice: Protective Role of Quercetin

Yang

Wang

Feei

et al. 2020

Molecular Nutrition Food Res

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Scope: Dietary advanced glycation products (dAGEs) have been reported to induce cognitive impairment while quercetin possesses potential neuroprotective effects. The aim is to explore whether dAGEs would induce similar cognitive impairment from both young and aged ICR mice, and the protective effects of quercetin. Methods and results: A total of 32 aged ICR mice (15-month-old) and 16 young ICR mice (3-month-old) are randomly assigned into the following six groups: Young mice control group, young mice fed with AGEs diet group, old mice control group, old mice fed with AGEs diet group, old mice with quercetin supplemented diet group, old mice fed with AGE diet supplemented with quercetin group. Dietary AGEs induced cognitive impairment only in aged, but not in young, ICR mice, while quercetin intervention is capable of reversing dAGEs-induced cognitive dysfunction. This may be since quercetin 1) increased miR-219, miR-15a, and miR-132 expression, inhibited p-ERK1/2, and tau phosphorylation; and 2) improved gut microbiota richness and diversity, inhibited phylum Tenericutes and Proteobacteria, and elevated butyric acid from cecum. Conclusion: Prolonged application of quercetin may be beneficial in the elderly, especially for those with high consumption of dAGEs.

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Section: Discussionmentioning

confidence: 73%

DietaryAdvancedGlycationEnd Products–InducedCognitive Impairment in Aged ICR Mice: Protective Role of Quercetin

Yang

Wang

Feei

et al. 2020

Molecular Nutrition Food Res

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“…However, the exact molecular mechanisms of miR‐34c and its upstream regulatory pathways in the development of AD have not yet been elucidated. Some functional miRNAs, including miR‐34 family, are differentially expressed in AD and cancer (Bhatnagar et al, ; Chamani, Sadeghizadeh, Masoumi, & Babashah, ; El Fatimy et al, ). We speculate that the tumor suppressor miR‐34c might play a role in the inverse relationship between AD and cancer.…”

Section: Introductionmentioning

confidence: 99%

Increased miR‐34c mediates synaptic deficits by targeting synaptotagmin 1 through ROS‐JNK‐p53 pathway in Alzheimer’s Disease

Shi

Zhang

Zhou³

et al. 2020

Aging Cell

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Alzheimer's disease (AD) and cancer have inverse relationship in many aspects. Some tumor suppressors, including miR‐34c, are decreased in cancer but increased in AD. The upstream regulatory pathways and the downstream mechanisms of miR‐34c in AD remain to be investigated. The expression of miR‐34c was detected by RT–qPCR in oxidative stressed neurons, hippocampus of SAMP8 mice, or serum of patients with amnestic mild cognitive impairment (aMCI). Dual luciferase assay was performed to confirm the binding sites of miR‐34c in its target mRNA. The Morris water maze (MWM) was used to evaluate learning and memory in SAMP8 mice administrated with miR‐34c antagomir (AM34c). Golgi staining was used to evaluate the synaptic function and structure. The dramatically increased miR‐34c was mediated by ROS‐JNK‐p53 pathway and negatively regulated synaptotagmin 1 (SYT1) expression by targeting the 3′‐untranslated region (3′‐UTR) of syt1 in AD. The expression of SYT1 protein was reduced by over expression of miR‐34c in the HT‐22 cells and vice versa. Administration of AM34c by the third ventricle injection or intranasal delivery markedly increased the brain levels of SYT1 and ameliorated the cognitive function in SAMP8 mice. The serum miR‐34c was significantly increased in patients with aMCI and might be a predictive biomarker for diagnosis of aMCI. These results indicated that increased miR‐34c mediated synaptic and memory deficits by targeting SYT1 through ROS‐JNK‐p53 pathway and the miR‐34c/SYT1 pathway could be considered as a promising novel therapeutic target for patients with AD.

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“…Therefore, miR-132 functions as a key activity-dependent regulator of cognition, whose expression must be maintained within a limited range to ensure normal learning and memory formation [48]. In fact, miR-132 has been considered as a master regulator of neuronal health [49], and its supplementation is being evaluated for the treatment of diseases such as tau-associated neurodegenerative disorders [50]. Therefore, in an analogous way, miR-148b-3p might also play a role in the protection of the central nervous system.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-148b-3p and MicroRNA-25-3p Are Overexpressed in Fetuses with Late-Onset Fetal Growth Restriction

et al. 2020

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Objective: It was the aim of this study to describe a micro-RNA (miRNA) profile characteristic of late-onset fetal growth restriction (FGR) and to investigate the pathways involved in their biochemical action. Methods: In this prospective study, 25 fetuses (16 normal and 9 with FGR [estimated fetal weight < 10th centile plus cerebroplacental ratio < 0.6765 multiples of the median]) were evaluated with Doppler ultrasound after 36 weeks. Afterwards, for every fetus, plasma from umbilical vein blood was collected at birth, miRNA was extracted, and full miRNA sequencing was performed. Subsequently, comparisons were done in order to obtain those miRNAs that were differentially expressed. Results: The FGR fetuses expressed upregulation of two miRNAs: miR-25-3p and, especially, miR-148b-3p, a miRNA directly involved in Schwann cell migration, neuronal plasticity, and energy metabolism (p = 0.0072, p = 0.0013). Conclusions: FGR fetuses express a different miRNA profile, which includes overexpression of miR-25-3p and miR-148b-3p. This information might improve our understanding of the pathophysiological processes involved in late-onset FGR. Future validation and feasibility studies will be required to propose miRNAs as a valid tool in the diagnosis and management of FGR.

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MicroRNA-132 provides neuroprotection for tauopathies via multiple signaling pathways

Cited by 110 publications

References 71 publications

DietaryAdvancedGlycationEnd Products–InducedCognitive Impairment in Aged ICR Mice: Protective Role of Quercetin

DietaryAdvancedGlycationEnd Products–InducedCognitive Impairment in Aged ICR Mice: Protective Role of Quercetin

Increased miR‐34c mediates synaptic deficits by targeting synaptotagmin 1 through ROS‐JNK‐p53 pathway in Alzheimer’s Disease

MicroRNA-148b-3p and MicroRNA-25-3p Are Overexpressed in Fetuses with Late-Onset Fetal Growth Restriction

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