Skip to content

Loss of MicroRNA-7 Regulation Leads to α-Synuclein Accumulation and Dopaminergic Neuronal Loss In Vivo

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)2404-2414
Number of pages11
JournalMolecular Therapy
Volume25
Issue number10
Early online date31 Aug 2017
DOIs
DateAccepted/In press - 24 Aug 2017
DateE-pub ahead of print - 31 Aug 2017
DatePublished (current) - 4 Oct 2017

Abstract

Abnormal alpha-synuclein (α-synuclein) expression and aggregation is a key characteristic of Parkinson's disease (PD). However, the exact mechanism(s) linking α-synuclein to the other central feature of PD, dopaminergic neuron loss, remains unclear. Therefore, improved cell and in vivo models are needed to investigate the role of α-synuclein in dopaminergic neuron loss. MicroRNA-7 (miR-7) regulates α-synuclein expression by binding to the 3' UTR of the Synuclein Alpha Non A4 Component of Amyloid Precursor (SNCA) gene and inhibiting its translation. We show that miR-7 is decreased in the substantia nigra of patients with PD and, therefore, may play an essential role in the regulation of α-synuclein expression. Furthermore, we have found that lentiviral-mediated expression of miR-7 complementary binding sites to stably induce a loss of miR-7 function results in an increase in α-synuclein expression in vitro and in vivo. We have also shown that depletion of miR-7 using a miR-decoy produces a loss of nigral dopaminergic neurons accompanied by a reduction of striatal dopamine content. These data suggest that miR-7 has an important role in the regulation of α-synuclein and dopamine physiology and may provide a new paradigm to study the pathology of PD.

    Research areas

  • Parkinson’s disease, α-synuclein, microRNA, microRNA-7, lentiviral vector

Download statistics

No data available

Documents

Documents

  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Cell Press at https://www.sciencedirect.com/science/article/pii/S1525001617303799 . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 363 KB, PDF document

    Licence: CC BY-NC-ND

  • Supplementary information PDF Figures 1 -6

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Cell Press at https://www.sciencedirect.com/science/article/pii/S1525001617303799 . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 1 MB, PDF document

    Licence: CC BY-NC-ND

DOI

View research connections

Related faculties, schools or groups