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Open Access Research

microRNA-128a dysregulation in transgenic Huntington’s disease monkeys

Jannet Kocerha123, Yan Xu12, Melinda S Prucha12, Dongming Zhao12 and Anthony WS Chan12*

  • * Corresponding author: Anthony WS Chan awchan@emory.edu

  • † Equal contributors

Author Affiliations

1 Division of Neuropharmacology and Neurologic Disease, Yerkes National Primate Research Center, 954 Gatewood Rd., N.E Atlanta, GA 30329, USA

2 Department of Human Genetics, Emory University School of Medicine, 615 Michael St., Whitehead Building, Atlanta, GA 30322, USA

3 Current address: Department of Chemistry, Georgia Southern University, Statesboro, GA 30458, USA

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Molecular Brain 2014, 7:46  doi:10.1186/1756-6606-7-46

Published: 13 June 2014

Abstract

Background

Huntington’s Disease (HD) is a progressive neurodegenerative disorder with a single causal mutation in the Huntingtin (HTT) gene. MicroRNAs (miRNAs) have recently been implicated as epigenetic regulators of neurological disorders, however, their role in HD pathogenesis is not well defined. Here we study transgenic HD monkeys (HD monkeys) to examine miRNA dysregulation in a primate model of the disease.

Results

In this report, 11 miRNAs were found to be significantly associated (P value < 0.05) with HD in the frontal cortex of the HD monkeys. We further focused on one of those candidates, miR-128a, due to the corresponding disruption in humans and mice with HD as well as its intriguing lists of gene targets. miR-128a was downregulated in our HD monkey model by the time of birth. We then confirmed that miR-128a was also downregulated in the brains of pre-symptomatic and post-symptomatic HD patients. Additionally, our studies confirmed a panel of canonical HD signaling genes regulated by miR-128a, including HTT and Huntingtin Interaction Protein 1 (HIP1).

Conclusion

Our studies found that miR-128a may play a critical role in HD and could be a viable candidate as a therapeutic or biomarker of the disease.

Keywords:
microRNAs; Noncoding RNAs; Huntington’s disease; Brain; miR-128a