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Review
. 2017 Feb 19;483(4):1156-1165.
doi: 10.1016/j.bbrc.2016.08.067. Epub 2016 Aug 12.

A critical evaluation of neuroprotective and neurodegenerative MicroRNAs in Alzheimer's disease

P Hemachandra Reddy  1 , Sahil Tonk  2 , Subodh Kumar  2 , Murali Vijayan  2 , Ramesh Kandimalla  2 , Chandra Sekhar Kuruva  2 , Arubala P Reddy  3
Affiliations
Review

A critical evaluation of neuroprotective and neurodegenerative MicroRNAs in Alzheimer's disease

P Hemachandra Reddy et al. Biochem Biophys Res Commun. .

Abstract

Currently, 5.4 million Americans suffer from AD, and these numbers are expected to increase up to 16 million by 2050. Despite tremendous research efforts, we still do not have drugs or agents that can delay, or prevent AD and its progression, and we still do not have early detectable biomarkers for AD. Multiple cellular changes have been implicated in AD, including synaptic damage, mitochondrial damage, production and accumulation of Aβ and phosphorylated tau, inflammatory response, deficits in neurotransmitters, deregulation of the cell cycle, and hormonal imbalance. Research into AD has revealed that miRNAs are involved in each of these cellular changes and interfere with gene regulation and translation. Recent discoveries in molecular biology have also revealed that microRNAs play a major role in post-translational regulation of gene expression. The purpose of this article is to review research that has assessed neuroprotective and neurodegenerative characteristics of microRNAs in brain samples from AD transgenic mouse models and patients with AD.

Keywords: Alzheimer's disease; Mitochondrial dysfunction; Phosphorylated tau; Synaptic damage; microRNAs.

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Figures

Figure 1
Figure 1. Hypothesized miRNA biogenesis pathway
miRNA biogenesis initiates in the nucleus with transcription of primary miRNA transcripts from miRNA coding genes by RNA Polymerase II or III. pri-miRNA converted to hair-pin loop pre-miRNA by enzymatic digestion with Drosha and DGCR8 proteins. Pre-miRNA is transported to the cytoplasm by Exportin-5/Ran/GTP proteins and is digested by the cytoplasmic proteins Dicer/TRBP and generates miRNA duplex. The duplex structure is unwound by helicase, and a mature miRNA strand is generated. Mature miRNAs form the RISC complex with the Ago2 protein. The mature miRNAs target the 3′UTR of mRNA and modulate gene activity either by suppressing mRNA cleavage or the translation.
Figure 2
Figure 2. AD risk factors and associated miRNAs
Deregulation of miRNAs expression modulates the expression of certain key AD related genes and promote disease progression. Beside miRNAs also involved in several cellular process that are critical for AD.
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