Loss of microRNA-7 leads to alpha synuclein accumulation and dopaminergic neuronal loss in vivo

Oscar Cordero Llana*, Kirsty J McMillan, Tracey K. Murray, Nora Bengoa-Vergniory, Jane Cooper, Amy Buckley, Richard Wade-Martins, James B Uney, Michael J O'Neill, Liang-Fong Wong, Maeve A Caldwell*

*Corresponding author for this work

Research output: Contribution to conferenceConference Abstractpeer-review

Abstract

Abnormal alpha synuclein (α-syn) expression and aggregation are key characteristics of Parkinson’s. However, the exact mechanisms linking α-syn to dopaminergic neuron loss, remain unclear. MicroRNA-7 (miR-7) regulates α-syn expression by binding to the 3’ untranslated region (UTR) of the SNCA gene and inhibiting its translation. miR-7 is decreased in the substantia nigra of patients with Parkinson’s and therefore may play an essential role in the regulation of α-syn expression. Lentiviral mediated expression of miR-7 complementary binding sites to stably induce a loss of miR-7 function results in an increase in α-syn 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-syn and dopamine physiology and may provide a new paradigm to study the pathology of Parkinson’s.
Original languageEnglish
Publication statusPublished - 2018
EventThe 41st Annual Meeting Japanese Neuroscience Society July 26-29, 2018 - Kobe Convention Center, Kobe, Japan
Duration: 26 Jul 201829 Jul 2018
http://www.jnss.org/abstract/neuro2018/meeting_planner/

Conference

ConferenceThe 41st Annual Meeting Japanese Neuroscience Society July 26-29, 2018
CountryJapan
CityKobe
Period26/07/1829/07/18
Internet address

Keywords

  • Parkinson’s disease
  • microRNAs
  • microRNA-7
  • α-synuclein
  • viral vector

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