title: Inhibition of miR-34b and miR-34c enhances α-synuclein expression in Parkinson's disease.
abstract: Mounting evidence suggests that microRNA (miR) dysregulation contributes to neurodegenerative disorders including Parkinson's disease (PD). MiR-34b and miR-34c have been previously shown to be down-regulated in the brains of patients with PD. Here, we demonstrate that miR-34b and miR-34c repress the expression of α-synuclein (α-syn), a key protein in PD pathogenesis. Inhibition of miR-34b and miR-34c expression in human dopaminergic SH-SY5Y cells increased α-syn levels and stimulated aggregate formation. Additionally, a single nucleotide polymorphism (SNP) in the 3'-UTR of α-syn was found to lower the miR-34b-mediated repression of the protein. Our results suggest that down-regulation of miR-34b and miR-34c in the brain, as well as an SNP in the 3'-UTR of α-syn can increase α-syn expression, possibly contributing to PD pathogenesis.
authors.affiliation: Center for Neurodegenerative and Neuroimmunologic Diseases, Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
authors.forename: Savan
authors.initials: S
authors.lastname: Kabaria
authors.affiliation: Center for Neurodegenerative and Neuroimmunologic Diseases, Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
authors.forename: Doo Chul
authors.initials: DC
authors.lastname: Choi
authors.affiliation: Center for Neurodegenerative and Neuroimmunologic Diseases, Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
authors.forename: Amrita Datta
authors.initials: AD
authors.lastname: Chaudhuri
authors.affiliation: Center for Neurodegenerative and Neuroimmunologic Diseases, Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
authors.forename: M Maral
authors.initials: MM
authors.lastname: Mouradian
authors.affiliation: Center for Neurodegenerative and Neuroimmunologic Diseases, Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. Electronic address: junneu@rwjms.rutgers.edu.
authors.forename: Eunsung
authors.initials: E
authors.lastname: Junn
mesh_terms: D020413:3' Untranslated Regions; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D051844:alpha-Synuclein / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D051844:alpha-Synuclein
keywords: Parkinson’s disease; microRNA-34b; microRNA-34c; α-Synuclein