Inhibition of miR-34b and miR-34c enhances α-synuclein expression in Parkinson's disease

Savan Kabaria, Doo Chul Choi, Amrita Datta Chaudhuri, M Maral Mouradian, Eunsung Junn

Research output: Contribution to journalArticle

75 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)319-325
Number of pages7
JournalFEBS Letters
Volume589
Issue number3
DOIs
StatePublished - Jan 30 2015

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Keywords

  • Parkinson' disease
  • microRNA-34b
  • microRNA-34c
  • α-Synuclein

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