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MicroRNAs as the cause of schizophrenia in 22q11.2 deletion carriers, and possible implications for idiopathic disease: a mini-review
The 22q11.2 deletion is the strongest known genetic risk factor for schizophrenia. Research has implicated microRNA-mediated dysregulation in 22q11.2 deletion syndrome (22q11.2DS) schizophrenia-risk. Primary candidate genes are DGCR8 (DiGeorge syndrome critical region gene 8), which encodes a compon...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2013
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851736/ https://www.ncbi.nlm.nih.gov/pubmed/24367288 http://dx.doi.org/10.3389/fnmol.2013.00047 |
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author | Forstner, Andreas J. Degenhardt, Franziska Schratt, Gerhard Nöthen, Markus M. |
author_facet | Forstner, Andreas J. Degenhardt, Franziska Schratt, Gerhard Nöthen, Markus M. |
author_sort | Forstner, Andreas J. |
collection | PubMed |
description | The 22q11.2 deletion is the strongest known genetic risk factor for schizophrenia. Research has implicated microRNA-mediated dysregulation in 22q11.2 deletion syndrome (22q11.2DS) schizophrenia-risk. Primary candidate genes are DGCR8 (DiGeorge syndrome critical region gene 8), which encodes a component of the microprocessor complex essential for microRNA biogenesis, and MIR185, which encodes microRNA 185. Mouse models of 22q11.2DS have demonstrated alterations in brain microRNA biogenesis, and that DGCR8 haploinsufficiency may contribute to these alterations, e.g., via down-regulation of a specific microRNA subset. miR-185 was the top-scoring down-regulated microRNA in both the prefrontal cortex and the hippocampus, brain areas which are the key foci of schizophrenia research. This reduction in miR-185 expression contributed to dendritic and spine development deficits in hippocampal neurons. In addition, miR-185 has two validated targets (RhoA, Cdc42), both of which have been associated with altered expression levels in schizophrenia. These combined data support the involvement of miR-185 and its down-stream pathways in schizophrenia. This review summarizes evidence implicating microRNA-mediated dysregulation in schizophrenia in both 22q11.2DS-related and idiopathic cases. |
format | Online Article Text |
id | pubmed-3851736 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-38517362013-12-23 MicroRNAs as the cause of schizophrenia in 22q11.2 deletion carriers, and possible implications for idiopathic disease: a mini-review Forstner, Andreas J. Degenhardt, Franziska Schratt, Gerhard Nöthen, Markus M. Front Mol Neurosci Neuroscience The 22q11.2 deletion is the strongest known genetic risk factor for schizophrenia. Research has implicated microRNA-mediated dysregulation in 22q11.2 deletion syndrome (22q11.2DS) schizophrenia-risk. Primary candidate genes are DGCR8 (DiGeorge syndrome critical region gene 8), which encodes a component of the microprocessor complex essential for microRNA biogenesis, and MIR185, which encodes microRNA 185. Mouse models of 22q11.2DS have demonstrated alterations in brain microRNA biogenesis, and that DGCR8 haploinsufficiency may contribute to these alterations, e.g., via down-regulation of a specific microRNA subset. miR-185 was the top-scoring down-regulated microRNA in both the prefrontal cortex and the hippocampus, brain areas which are the key foci of schizophrenia research. This reduction in miR-185 expression contributed to dendritic and spine development deficits in hippocampal neurons. In addition, miR-185 has two validated targets (RhoA, Cdc42), both of which have been associated with altered expression levels in schizophrenia. These combined data support the involvement of miR-185 and its down-stream pathways in schizophrenia. This review summarizes evidence implicating microRNA-mediated dysregulation in schizophrenia in both 22q11.2DS-related and idiopathic cases. Frontiers Media S.A. 2013-12-05 /pmc/articles/PMC3851736/ /pubmed/24367288 http://dx.doi.org/10.3389/fnmol.2013.00047 Text en Copyright © 2013 Forstner, Degenhardt, Schratt and Nöthen. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Forstner, Andreas J. Degenhardt, Franziska Schratt, Gerhard Nöthen, Markus M. MicroRNAs as the cause of schizophrenia in 22q11.2 deletion carriers, and possible implications for idiopathic disease: a mini-review |
title | MicroRNAs as the cause of schizophrenia in 22q11.2 deletion carriers, and possible implications for idiopathic disease: a mini-review |
title_full | MicroRNAs as the cause of schizophrenia in 22q11.2 deletion carriers, and possible implications for idiopathic disease: a mini-review |
title_fullStr | MicroRNAs as the cause of schizophrenia in 22q11.2 deletion carriers, and possible implications for idiopathic disease: a mini-review |
title_full_unstemmed | MicroRNAs as the cause of schizophrenia in 22q11.2 deletion carriers, and possible implications for idiopathic disease: a mini-review |
title_short | MicroRNAs as the cause of schizophrenia in 22q11.2 deletion carriers, and possible implications for idiopathic disease: a mini-review |
title_sort | micrornas as the cause of schizophrenia in 22q11.2 deletion carriers, and possible implications for idiopathic disease: a mini-review |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851736/ https://www.ncbi.nlm.nih.gov/pubmed/24367288 http://dx.doi.org/10.3389/fnmol.2013.00047 |
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