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A microRNA-based gene dysregulation pathway in Huntington's disease

Johnson, Rory, Zuccato, Chiara, Belyaev, Nikolai D., Guest, Deborah J., Cattaneo, Elena, Buckley, Noel J.·2008·Neurobiology of Disease
DOI 10.1016/j.nbd.2007.11.001
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Abstract

Huntington's disease (HD) is a dominantly-inherited neurodegenerative disorder which is incurable and ultimately fatal. HD is characterised by widespread mRNA dysregulation, particularly in neurons of the forebrain, by mechanisms which are not fully understood. Such dysregulation has been demonstrated to result, in part, from aberrant nuclear localisation of the transcriptional repressor, REST. Here, we show that expression of a number of neuronal-specific microRNAs is also dysregulated in HD tissues, probably as a result of increased repression by REST. This phenomenon is observed in both murine models of HD and in the brains of human HD sufferers. MicroRNA loss is reflected in increased levels of a number of target messenger RNAs. These data are the first to demonstrate a role for microRNAs in HD, and indicate that the molecular aetiology of HD is reflected in a loss of neuronal identity, caused in part by dysregulation of both transcriptional and post-transcriptional mechanisms.

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Metadata

Authors
Johnson, R., Zuccato, C., Belyaev, N. D., Guest, D. J., Cattaneo, E., & Buckley, N. J.
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2008-03
Volume
29
Issue
3
Pages
438-445
ISSN
0969-9961
DOI
10.1016/j.nbd.2007.11.001
Cited by
312
References
2
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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