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
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
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...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
-
Strategies for Targeting Lentiviral Vectors
Current Gene Therapy The HGF-Met Signaling Axis: Emerging Themes and Targets of Inhibition
Current Protein & Peptide Science Modified Polysaccharides as Carriers for Biomolecules
Pharmaceutical Nanotechnology Gynaecological Cancer Diagnostics: 99mTc-Cisplatin Complex as a Future Approach for Early, Prompt and Efficient Diagnosis of Gynaecological Cancer
Current Medical Imaging Cancer Diagnosis and Treatment Guidance: Role of MRI and MRI Probes in the Era of Molecular Imaging
Current Pharmaceutical Biotechnology Nanoparticle Based Delivery of Protease Inhibitors to Cancer Cells
Current Medicinal Chemistry Antibody-Drug Conjugate Targets
Current Cancer Drug Targets Screening Neuroprotective Agents Through 4-hydroxynonenal, Ethanol, High Glucose, Homocysteine, Okadaic Acid, Rotenone, and Oxygen-Glucose Deprivation Induced PC12 Injury Models: A Review
Current Psychopharmacology Resistance to Anti-VEGF Agents
Current Pharmaceutical Design Potential Cardio-Protective Agents: A Resveratrol Review (2000-2019)
Current Pharmaceutical Design Cancer: A Problem of Developmental Biology; Scientific Evidence for Reprogramming and Differentiation Therapy
Current Drug Targets MicroRNA-208a Potentiates Angiotensin II-triggered Cardiac Myoblasts Apoptosis via Inhibiting Nemo-like Kinase (NLK)
Current Pharmaceutical Design Hybrid PET/MRI for In Vivo Imaging of Cancer: Current Clinical Experiences and Recent Advances
Current Medical Imaging Polyethyleneimine-Based Nanocarriers for Gene Delivery
Current Pharmaceutical Design Quantification of Rat Brain Amino Acids: Analysis of the Data Consistency
Current Analytical Chemistry Astatine Radiopharmaceuticals: Prospects and Problems
Current Radiopharmaceuticals Unraveling the Action Mechanism of Buyang Huanwu Tang (BYHWT) for Cerebral Ischemia by Systematic Pharmacological Methodology
Combinatorial Chemistry & High Throughput Screening Multiple Sclerosis, Gut Microbiota and Permeability: Role of Tryptophan Catabolites, Depression and the Driving Down of Local Melatonin
Current Pharmaceutical Design Protein Kinase C as a Drug Target Implications for Drug or Diet Prevention and Treatment of Cancer
Current Drug Targets Peptide Activators of the p53 Tumor Suppressor
Current Pharmaceutical Design