title: microRNA-128a dysregulation in transgenic Huntington's disease monkeys.
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).
  
  
  CONCLUSIONS
  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.
authors.forename: Jannet
authors.initials: J
authors.lastname: Kocerha
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Melinda S
authors.initials: MS
authors.lastname: Prucha
authors.forename: Dongming
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Division of Neuropharmacology and Neurologic Disease, Yerkes National Primate Research Center, 954 Gatewood Rd,, N,E Atlanta, GA 30329, USA. awchan@emory.edu.
authors.forename: Anthony W S
authors.initials: AW
authors.lastname: Chan
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D053148:Caspase 3 / Q000378:metabolism; D004789:Enzyme Activation; D005625:Frontal Lobe / Q000201:enzymology / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D060005:Genotyping Techniques; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D057809:HEK293 Cells; D000882:Haplorhini / Q000235:genetics*; D006801:Humans; D006816:Huntington Disease / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D020836:Protein Structure, Quaternary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D005904:Glial Fibrillary Acidic Protein; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D053148:Caspase 3