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

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.