Review Article
Alterations in micro RNA-messenger RNA (miRNA-mRNA) Coupled Signaling Networks in Sporadic Alzheimer's Disease (AD) Hippocampal CA1
Jaber V1, Zhao Y2and Lukiw WJ1,3*1LSU Neuroscience Center, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite 904, New Orleans LA 70112 USA
2Department of Cell Biology and Anatomy, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite 904, New Orleans LA 70112 USA
3Departments of Ophthalmology and Neurology, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite 904, New Orleans LA 70112 USA
- *Corresponding Author:
- Walter J Lukiw
Professor of Neuroscience, Neurology and Ophthalmology
Bollinger Professor of Alzheimer’s disease (AD)
LSU Neuroscience Center of Excellence
Louisiana State University Health Sciences Center
2020 Gravier Street, Suite 904, LA 70112 USA
Tel: 5045990842
E-mail: wlukiw@lsuhsc.edu
Received date: February 22, 2017; Accepted date: March 03, 2017; Published date: March 10, 2017
Citation: Jaber V, Zhao Y, Lukiw WJ (2017) Alterations in micro RNA-messenger RNA (miRNA-mRNA) Coupled Signaling Networks in Sporadic Alzheimer’s Disease (AD) Hippocampal CA1. J Alzheimers Dis Parkinsonism 7:312. doi: 10.4172/2161- 0460.1000312
Copyright: © 2017 Jaber V, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
RNA sequencing, DNA microfluidic array, LED-Northern, Western immunoassay and bioinformatics analysis have uncovered a small family of up-regulated human brain enriched microRNAs (miRNAs) and down-regulated messenger RNAs (mRNAs) in short post-mortem interval (PMI) sporadic Alzheimer’s disease (AD) brain. At the mRNA level, a large majority of the expression of human brain genes found to be down-regulated in sporadic AD appears to be a consequence of an up-regulation of a specific group of NF-kB-inducible microRNAs (miRNAs). This group of up-regulated miRNAs – including miRNA-34a and miRNA-146a - has strong, energetically favorable, complimentary RNA sequences in the 3’ untranslated regions (3’-UTR) of their target mRNAs which ultimately drive the down-regulation in the expression of certain essential brain genes. Interestingly, just 2 significantly up-regulated miRNAs - miRNA-34a and miRNA-146a – appear to down-regulate mRNA targets involved in synaptogenesis (SHANK3), phagocytosis deficits and tau pathology (TREM2), inflammation (CFH; complement factor H) and amyloidogenesis (TSPAN12), all of which are distinguishing pathological features characteristic of middle-to-late stage AD neuropathology. This paper reports the novel finding of parallel miRNA-34a and miRNA-146a up-regulation in sporadic AD hippocampal CA1 RNA pools and proposes an altered miRNA-mRNA coupled signaling network in AD, much of which is supported by current experimental findings in the recent literature (202 words).