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

Savan Kabaria1, Doo Chul Choi1, Amrita Datta Chaudhuri1

  • 1Center for Neurodegenerative and Neuroimmunologic Diseases, Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.

FEBS Letters
|December 27, 2014
PubMed

Insights

MicroRNA-34b and microRNA-34c (miR-34b/c) normally reduce alpha-synuclein (α-syn) protein levels. Their reduced expression in Parkinson's disease (PD) may increase α-syn, contributing to PD pathogenesis.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • MicroRNA (miR) dysregulation is implicated in neurodegenerative disorders like Parkinson's disease (PD).
  • MiR-34b and miR-34c are notably downregulated in the brains of PD patients.
  • Alpha-synuclein (α-syn) is a key protein involved in PD pathogenesis.

Purpose of the Study:

  • To investigate the role of miR-34b and miR-34c in regulating α-syn expression.
  • To explore the impact of miR-34b/c dysregulation and genetic variations on PD pathogenesis.

Main Methods:

  • Investigated the repressive effect of miR-34b and miR-34c on α-syn expression.
  • Utilized human dopaminergic SH-SY5Y cells to study the impact of miR-34b/c inhibition on α-syn levels and aggregation.
  • Analyzed the effect of a single nucleotide polymorphism (SNP) in the α-syn 3'-UTR on miR-34b-mediated repression.

Main Results:

  • MiR-34b and miR-34c were confirmed to repress α-syn expression.
  • Inhibition of miR-34b/c in cells led to increased α-syn levels and aggregate formation.
  • An SNP in the α-syn 3'-UTR reduced the repressive effect of miR-34b on α-syn.

Conclusions:

  • Downregulation of miR-34b/c and the presence of a specific α-syn SNP may increase α-syn expression.
  • These molecular changes potentially contribute to the pathogenesis of Parkinson's disease.
Keywords:
Parkinson’s diseasemicroRNA-34bmicroRNA-34cα-Synuclein

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