Abstract
Background: miR-146a and miR-155 are key regulators of the innate immune response. We hypothesized that an inflammation-mediated dysregulation of these miRNAs may occur in patients with Down syndrome (DS) and Alzheimer's disease (AD).
Methods: The miRNA expression patterns were investigated by in situ hybridization in developing hippocampus from controls, patients with DS and in adults with AD pathology (DS and sporadic AD; sAD). Quantitative real-time PCR was employed to evaluate the miRNA levels in the hippocampus of sAD and in mouse models of DS and AD. Both miRNAs were expressed in prenatal human hippocampus. In DS we detected increased miR-146a expression in reactive astrocytes. Increased expression of miR-146a was found in the hippocampus of sAD and negatively correlated with its target IRAK-1. APP/PS1 mice showed a significant increase in the expression of both miRNAs at 11-13 months of age as compared to WT and mice at 3 months. A negative correlation between miR-146a levels and its target TRAF6 was observed in both Ts65Dn and APP/PS1 mice.
Conclusion: These findings suggest a possible involvement of miR-146a and miR-155 in brain development and neurodegeneration. In particular, we provide evidence of a dysregulation of these two immunomodulatory miRNAs in AD with a potential therapeutical implication, deserving further investigation.
Keywords: Hippocampus, development, Down's syndrome, Alzheimer's disease, Ts65Dn- APP/PS1, microRNAs.
Current Alzheimer Research
Title:Developmental Expression and Dysregulation of miR-146a and miR-155 in Down's Syndrome and Mouse Models of Down's Syndrome and Alzheimer's Disease
Volume: 14 Issue: 12
Author(s): A. Arena, A. M. Iyer, I. Milenkovic, G. G. Kovacs, I. Ferrer, M. Perluigi and E. Aronica*
Affiliation:
- Department of (Neuro) Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam,Netherlands
Keywords: Hippocampus, development, Down's syndrome, Alzheimer's disease, Ts65Dn- APP/PS1, microRNAs.
Abstract: Background: miR-146a and miR-155 are key regulators of the innate immune response. We hypothesized that an inflammation-mediated dysregulation of these miRNAs may occur in patients with Down syndrome (DS) and Alzheimer's disease (AD).
Methods: The miRNA expression patterns were investigated by in situ hybridization in developing hippocampus from controls, patients with DS and in adults with AD pathology (DS and sporadic AD; sAD). Quantitative real-time PCR was employed to evaluate the miRNA levels in the hippocampus of sAD and in mouse models of DS and AD. Both miRNAs were expressed in prenatal human hippocampus. In DS we detected increased miR-146a expression in reactive astrocytes. Increased expression of miR-146a was found in the hippocampus of sAD and negatively correlated with its target IRAK-1. APP/PS1 mice showed a significant increase in the expression of both miRNAs at 11-13 months of age as compared to WT and mice at 3 months. A negative correlation between miR-146a levels and its target TRAF6 was observed in both Ts65Dn and APP/PS1 mice.
Conclusion: These findings suggest a possible involvement of miR-146a and miR-155 in brain development and neurodegeneration. In particular, we provide evidence of a dysregulation of these two immunomodulatory miRNAs in AD with a potential therapeutical implication, deserving further investigation.
Export Options
About this article
Cite this article as:
Arena A. , Iyer M. A., Milenkovic I. , Kovacs G. G. , Ferrer I. , Perluigi M. and Aronica E. *, Developmental Expression and Dysregulation of miR-146a and miR-155 in Down's Syndrome and Mouse Models of Down's Syndrome and Alzheimer's Disease, Current Alzheimer Research 2017; 14 (12) . https://dx.doi.org/10.2174/1567205014666170706112701
DOI https://dx.doi.org/10.2174/1567205014666170706112701 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Alzheimer's Disease Drug Development
Alzheimer's disease is a progressive neurodegenerative disorder that affects millions of people worldwide. Despite decades of research, no cure or disease-modifying treatment is available yet. Therefore, the need for developing effective therapies to treat Alzheimer's disease is an urgent matter. This special issue aims to provide a comprehensive overview of ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Restoring TRAIL Induced Apoptosis Using Naturopathy. Hercules Joins Hand with Nature to Triumph Over Lernaean Hydra
Current Genomics The Autism Candidate Gene Neurobeachin Encodes a Scaffolding Protein Implicated in Membrane Trafficking and Signaling
Current Molecular Medicine Current Clinical Applications of In Vivo Magnetic Resonance Spectroscopy and Spectroscopic Imaging
Current Medical Imaging Magnetic Nanoparticles for MRI of Brain Tumors
Current Pharmaceutical Biotechnology Interpreting the Mechanisms by which Integrins Promote the Differentiation of Mesenchymal Stem Cells and Integrin Application Prospects
Current Stem Cell Research & Therapy GRP78 Influences Chemoresistance and Prognosis in Cancer
Current Drug Targets Wnt/beta-Catenin Signaling and Small Molecule Inhibitors
Current Pharmaceutical Design Clinical Studies with Targeted Toxins in Malignant Glioma
Reviews on Recent Clinical Trials Targeted Radiotherapy for Malignant Gliomas
Current Drug Discovery Technologies 1-Cyclohexylpiperazine and 3,3-Dimethylpiperidine Derivatives as Sigma-1 (σ1) and Sigma-2 (σ2) Receptor Ligands: A Review
Central Nervous System Agents in Medicinal Chemistry Targeting Chk2 Kinase: Molecular Interaction Maps and Therapeutic Rationale
Current Pharmaceutical Design Advances in Oncolytic Virus Therapy for Glioma
Recent Patents on CNS Drug Discovery (Discontinued) Focus on the Multimodal Role of Biomarkers in Breast Cancer
Current Pharmaceutical Design In Silico Prediction Models for Blood-Brain Barrier Permeation
Current Medicinal Chemistry Beyond the "Lock and Key" Paradigm: Targeting Lipid Rafts to Induce the Selective Apoptosis of Cancer Cells
Current Medicinal Chemistry Genes Involved in Apoptosis Regulation: Implications for Cancer Therapy
Current Genomics Erythrocyte-cancer Hybrid Membrane-camouflaged Mesoporous Silica Nanoparticles Loaded with Gboxin for Glioma-targeting Therapy
Current Pharmaceutical Biotechnology Pregnancy, Programming and Preeclampsia: Gap Junctions at the Nexus of Pregnancy-induced Adaptation of Endothelial Function and Endothelial Adaptive Failure in PE
Current Vascular Pharmacology Immune Checkpoint Regulators: A New Era Toward Promising Cancer Therapy
Current Cancer Drug Targets Novel Therapies Against Aggressive and Recurrent Epithelial Cancers by Molecular Targeting Tumor- and Metastasis-Initiating Cells and Their Progenies
Anti-Cancer Agents in Medicinal Chemistry