Frontotemporal Lobar Degeneration and MicroRNAs

Albani, Diego; Castellano, Anna Elisa; Forloni, Gianluigi; Confaloni, Annamaria

doi:10.3389/fnagi.2016.00017

Cited by 24 publications

(16 citation statements)

References 75 publications

(81 reference statements)

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“…Different studies showed that miRNAs are playing an important role in FTD pathology [11,12]. For example, several reports have evaluated miRNAs regulation of the progranulin gene, suggesting that it is under their control, as described for miR-29b, miR-107 and miR-659 [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Circulating miR-127-3p as a Potential Biomarker for Differential Diagnosis in Frontotemporal Dementia

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et al. 2018

JAD

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Given the heterogeneous nature of frontotemporal dementia (FTD), sensitive biomarkers are greatly needed for the accurate diagnosis of this neurodegenerative disorder. Circulating miRNAs have been reported as promising biomarkers for neurodegenerative disorders and processes affecting the central nervous system, especially in aging. The objective of the study was to evaluate if some circulating miRNAs linked with apoptosis (miR-29b-3p, miR-34a-5p, miR-16-5p, miR-17-5p, miR-107, miR-19b-3p, let-7b-5p, miR-26b-5p, and 127-3p) were able to distinguish between FTD patients and healthy controls. For this study, we enrolled 127 subjects, including 54 patients with FTD, 20 patients with Alzheimer's disease (AD), and 53 healthy controls. The qRT-PCR analysis showed a downregulation of miR-127-3p in FTD compared to controls, while the levels of other miRNAs remained unchanged. Then, miR-127-3p expression was also analyzed in AD patients, finding a different expression between two patient groups. A receiver operating characteristic curve was then created for miR-127-3p to discriminate FTD versus AD (AUC: 0.8986), and versus healthy controls (AUC: 0.8057). In conclusion, miR-127-3p could help to diagnose FTD and to distinguish it from AD.

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Section: Introductionmentioning

confidence: 99%

Circulating miR-127-3p as a Potential Biomarker for Differential Diagnosis in Frontotemporal Dementia

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et al. 2018

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“…FTLD shows several distinct clinical presentations differing not only among mutations but also within a single mutation and even within individual families, suggesting the involvement of post-transcriptional regulation mechanisms. Recent findings suggest that GRN is under the control of miRNAs (Piscopo et al, 2016 ). In FTLD patients with a common genetic variant of GRN (rs5848), it has been previously observed that there is a nucleotide substitution from C- to T-allele in the miR-659-3p binding site that should strengthen the binding of miR-659-3p to the GRN mRNA (Rademakers et al, 2008 ).…”

Section: Introductionmentioning

confidence: 99%

Reduced miR-659-3p Levels Correlate with Progranulin Increase in Hypoxic Conditions: Implications for Frontotemporal Dementia

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Crestini

et al. 2016

Front. Mol. Neurosci.

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Progranulin (PGRN) is a secreted protein expressed ubiquitously throughout the body, including the brain, where it localizes in neurons and is activated microglia. Loss-of-function mutations in the GRN gene are an important cause of familial frontotemporal lobar degeneration (FTLD). PGRN has a neurotrophic and anti-inflammatory activity, and it is neuroprotective in several injury conditions, such as oxygen or glucose deprivation, oxidative injury, and hypoxic stress. Indeed, we have previously demonstrated that hypoxia induces the up-regulation of GRN transcripts. Several studies have shown microRNAs (miRNAs) involvement in hypoxia. Moreover, in FTLD patients with a genetic variant of GRN (rs5848), the reinforcement of miR-659-3p binding site has been suggested to be a risk factor. Here, we report that miR-659-3p interacts directly with GRN 3′UTR as shown by luciferase assay in HeLa cells and ELISA and Western Blot analysis in HeLa and Kelly cells. Moreover, we demonstrate the physical binding between GRN mRNA and miR-659-3p employing a miRNA capture-affinity technology in SK-N-BE and Kelly cells. In order to study miRNAs involvement in hypoxia-mediated up-regulation of GRN, we evaluated miR-659-3p levels in SK-N-BE cells after 24 h of hypoxic treatment, finding them inversely correlated to GRN transcripts. Furthermore, we analyzed an animal model of asphyxia, finding that GRN mRNA levels increased at post-natal day (pnd) 1 and pnd 4 in rat cortices subjected to asphyxia in comparison to control rats and miR-659-3p decreased at pnd 4 just when GRN reached the highest levels. Our results demonstrate the interaction between miR-659-3p and GRN transcript and the involvement of miR-659-3p in GRN up-regulation mediated by hypoxic/ischemic insults.

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“…They are key regulators of many biological functions such as neurogenesis, dendritic spine morphology, and synaptic plasticity. Moreover there is increasing evidence for their role in neurodegenerative disorders [ 7 ]. Many studies investigated the correlation of miRNAs dysregulation with AD.…”

Section: Introductionmentioning

confidence: 99%

Plasma microRNAs biomarkers in mild cognitive impairment among patients with type 2 diabetes mellitus

et al. 2020

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Objectives To assess the potential value of some miRNAs as diagnostic biomarkers for mild cognitive impairment (MCI) among patients with type2 diabetes mellitus (T2DM) and to identify other risk factors for MCI among them. Methods This study enrolled 163 adults with T2DM using face to face interview. Cognitive function with its domains was assessed using Adenbrooke’s Cognitive Examination III (ACE III). Lipid profile, glycated hemoglobin, and miR-128, miR-132, miR- 874, miR-134, miR-323, and miR-382 expressions, using quantitative real-time PCR, were assessed. Results MCI was detected among 59/163 (36.2%) patients with T2DM. Plasma expression of miR-132 was significantly higher in T2DM patients with MCI compared to those without MCI and to normal cognitive healthy individuals (median = 2, 1.1 and 1.2 respectively, P < 0.05. Logistic regression analysis showed that higher miR-132 expression with adjusted odds ratio (AOR): 1.2 (95% CI 1.0–1.3), female gender (AOR:2.1; 95%CI 1.0–4.3), education below postgraduate (secondary and university education with AOR: 9.5 & 19.4 respectively) were the significant predicting factors for MCI among T2DM patients. Using ROC curve, miR-132 was the only assayed miRNA that significantly differentiates T2DM patients with MCI from those with normal cognition with 72.3% sensitivity, 56.2% specificity, and 63.8% accuracy (P < 0.05). Other studied miRNAs showed lower sensitivity and specificity for detecting MCI among studied T2DM participants. Conclusion MCI affects nearly one-third of adult patients with T2DM. A significantly over expression of miR-132 was detected among T2DM with MCI compared to those with normal cognition.

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Frontotemporal Lobar Degeneration and MicroRNAs

Cited by 24 publications

References 75 publications

Circulating miR-127-3p as a Potential Biomarker for Differential Diagnosis in Frontotemporal Dementia

Circulating miR-127-3p as a Potential Biomarker for Differential Diagnosis in Frontotemporal Dementia

Reduced miR-659-3p Levels Correlate with Progranulin Increase in Hypoxic Conditions: Implications for Frontotemporal Dementia

Plasma microRNAs biomarkers in mild cognitive impairment among patients with type 2 diabetes mellitus

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