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Emerging role of microRNAs in major depressive disorder: diagnosis and therapeutic implications
Open accessAbstract
Major depressive disorder (MDD) is a major public health concern. Despite tremendous advances, the pathogenic mechanisms associated with MDD are still unclear. Moreover, a significant number of MDD subjects do not respond to the currently available medication. MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by modulating translation, messenger RNA (mRNA) degradation, or stability of mRNA targets. The role of miRNAs in disease pathophysiology is emerging rapidly. Recent studies demonstrating the involvement of miRNAs in several aspects of neural plasticity, neurogenesis, and stress response, and more direct studies in human postmortem brain provide strong evidence that miRNAs can not only play a critical role in MDD pathogenesis, but can also open up new avenues for the development of therapeutic targets. Circulating miRNAs are now being considered as possible biomarkers in disease pathogenesis and in monitoring therapeutic responses because of the presence and/or release of miRNAs in blood cells as well as in other peripheral tissues. In this review, these aspects are discussed in a comprehensive and critical manner.
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![Figure 1. miRNA biogenesis. microRNAs (miRNAs) are encoded in the genome (inter or intragenis) and transcribed by RNA polymerase II (RNA pol II) to generate primary microRNA (pri-miRNA). These pri-miRNAs are taken up by the RNA II enzyme Drosha/DiGeorge syndrome critical region 8 (DGCR8) protein, which catalyzes the formation of precursor miRNA (pre-miRNA). Pre-miRNA is then exported to cytoplasm by ExportinB in conjunction with Ras-related nuclear protein, RanGTR In the cytoplasm, pre-miRNA is cleaved into miRNA:miRNA* duplex by the Rnase III enzyme Dicer/Tar RNA-binding protein (TRBP) or PKR activating protein (PACT). One of these miRNA/miRNA* duplexes is discarded and the other one is loaded onto an Argonaute (Ago) homologue protein (isoforms of eukaryotic translation initiation factor [eIF] 2c) to generate the effector complex, known as RNA-induced silencing complex (RISC). The RISC complex directs miRNA to specific “short-seed” sequences located predominantly within the 3' UTR region of the target messenger RNA (mRNA). This leads to degradation or translational inhibition. nt, nucleotides](/paper-figures/5fadb9242e35452c8c67b69c1f9083ab/emerging-role-of-micrornas-in-major-depressive-disorder-diagnosis-and-figure-1.jpg)
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“A common post-transcriptional process mediated at least in part by miRNA alters the structure of dendrites and neurogenesis.”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [140]
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“As already mentioned, actively secreted miRNAs are enclosed in exosomes, which are excreted in response to stress signaling (Mendell and Olson, 2012) and thus considered as potential biomarkers in depression and antidepressant response (Dwivedi, 2014).”
BackgroundInfluentialTreatment resistant depression: A multi-scale, systems biology approach
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Epigenetic mechanisms of major depression: Targeting neuronal plasticity
Uchida, S., Yamagata, H., Seki, T., & Watanabe, Y. (2018) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12621 · Cited by 181
Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression
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Metadata
- Authors
- Dwivedi, Y.
- Affiliations
- University of Alabama at Birmingham (US)
- Corresponding author
- Dwivedi, Yogesh
- ORCID
- Dwivedi, Yogesh
- Venue
- Dialogues in Clinical Neuroscience
- Publisher
- Informa UK Limited
- Published
- 2014-03-31
- Volume
- 16
- Issue
- 1
- Pages
- 43-61
- ISSN
- 1294-8322 (ISSN-L)
- 1958-5969
- PMC
- PMC3984890
- OpenAlex
- W2166817991
- Cited by
- 169
- References
- 196
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 12 · 2023: 9 · 2022: 13 · 2021: 23 · 2020: 20 · 2019: 15 · 2018: 15 · 2017: 21 · 2016: 10 · 2015: 12 · 2014: 3
- FWCI
- 4.91
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- Dialogues in Clinical Neuroscience (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UL1TR000050)
- National Institute of Mental Health (1R01MH0100616, R21MH081099, R01MH101890, R01MH082802, R01MH100616, R21MH091509)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- major depressive disorder, microRNA, circulating microRNAs, biomarkers, depression diagnosis, depression treatment response, postmortem brain, neuroplasticity, neurogenesis, stress response, therapeutic target, non-coding RNA
- MeSH terms
- Animals, Major Depressive Disorder, Humans, Neuronal Plasticity, Biomarkers, MicroRNAs, Neurogenesis
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