J Alzheimers Dis Parkinsonism. 2017 Apr;7(2). doi: 10.4172/2161-0460.1000312. Epub 2017 Mar 10.

Alterations in micro RNA-messenger RNA (miRNA-mRNA) Coupled Signaling Networks in Sporadic Alzheimer's Disease (AD) Hippocampal CA1.

Journal of Alzheimer's disease & Parkinsonism

V Jaber, Y Zhao, W J Lukiw

PMID: 29051843 PMCID: PMC5645033 DOI: 10.4172/2161-0460.1000312

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.

Keywords: Bioinformatics; DNA microfluidic array; Inflammation; Phagocytosis; Synaptogenesis; messenger RNA (mRNA); miRNA-146a; miRNA-34a; microRNA (miRNA)

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Publication Types

• Journal Article

Grant support

• R01 EY006311/EY/NEI NIH HHS/United States
• R01 AG018031/AG/NIA NIH HHS/United States
• P50 AG016573/AG/NIA NIH HHS/United States
• R01 AG038834/AG/NIA NIH HHS/United States
• P30 GM103340/GM/NIGMS NIH HHS/United States