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Review
. 2017 Feb 6:73:87-103.
doi: 10.1016/j.pnpbp.2016.03.010. Epub 2016 Apr 9.

Diagnostic and therapeutic potential of microRNAs in neuropsychiatric disorders: Past, present, and future

Begum Alural  1 , Sermin Genc  1 , Stephen J Haggarty  2
Affiliations
Review

Diagnostic and therapeutic potential of microRNAs in neuropsychiatric disorders: Past, present, and future

Begum Alural et al. Prog Neuropsychopharmacol Biol Psychiatry. .

Abstract

Neuropsychiatric disorders are common health problems affecting approximately 1% of the population. Twin, adoption, and family studies have displayed a strong genetic component for many of these disorders; however, the underlying pathophysiological mechanisms and neural substrates remain largely unknown. Given the critical need for new diagnostic markers and disease-modifying treatments, expanding the focus of genomic studies of neuropsychiatric disorders to include the role of non-coding RNAs (ncRNAs) is of growing interest. Of known types of ncRNAs, microRNAs (miRNAs) are 20-25-nucleotide, single-stranded, molecules that regulate gene expression through post-transcriptional mechanisms and have the potential to coordinately regulate complex regulatory networks. In this review, we summarize the current knowledge on miRNA alteration/dysregulation in neuropsychiatric disorders, with a special emphasis on schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). With an eye toward the future, we also discuss the diagnostic and prognostic potential of miRNAs for neuropsychiatric disorders in the context of personalized treatments and network medicine.

Keywords: Bipolar disorder; MiRNA; Neuroplasticity; Non-coding RNA; Schizophrenia.

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Figures

Fig. 1
Fig. 1
Overview of miRNA biogenesis and its interaction with FMRP. RNA polymerase transcribes the miRNA genes, and Drosha processes the resulting pri-miRNAs. Then, pre-miRNAs are exported into the cytoplasm and are further processed by Dicer. Mature miRNAs are loaded into the RISC, which in turns binds to complementary sequences on 3′UTRs of target mRNAs. According to an alternative hypothesis, FMRP binds to some mRNAs, and miRNA-RISC can interact with FMRP-mRNA complex, thereby leading to translational inhibition.
Fig. 2
Fig. 2
The effect of SNPs on miRNA-mediated regulation of gene expression. SNPs in different steps of miRNA biogenesis exert diverse effects on the regulation of gene expression. (A) SNPs in miRNA genes can alter miRNA expression. (B) SNPs in target mRNAs also affect miRNA function by altering miRNA-target interaction. (C) SNPs in miRNA machinery genes affect the entire transcriptome that is subject to miRNA-mediated regulation.
See this image and copyright information in PMC

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