Angiotensin-(1-7) relieves behavioral defects and a-synuclein expression through NEAT1/miR-153-3p axis in Parkinson's disease
Parkinson's disease is the second most common neurodegenerative disorder, whose characteristic pathology involves progressive loss of dopaminergic neurons and formation of Lewy bodies(LBs) in the substantia nigra(SN). Aggregated and misfolded a-synuclein(a-syn) is the major constituent of LBs. As the newly discovered pathway of renin-angiotensin system (RAS), Angiotensin-(1-7)(Ang-(1-7)) and its receptor Mas have attracted increasing attentions for their correlation with PD progression, but underlying mechanisms remain not very clear. Based on the above, this study established PD models of mice and primary dopaminergic neurons with overexpression of a-syn, then discussed the effect of Ang-(1-7)/Mas on these models combined with downstream lncRNA and miRNA. The findings show that Ang-(1-7) alleviates behavioral disorders, rescues dopaminergic neurons loss and lowers a-syn expression in the SN of ha-syn(A53T) overexpressed PD mice. We also discover that Ang-(1-7) decreases the level of a-syn and apoptosis in the ha-syn(A53T) overexpressed dopaminergic neurons through NEAT1/miR-153-3p axis. Moreover, miR-153-3p expression in peripheral blood is found negatively correlated with that of a-syn. These results not only uncovered the significance and related mechanisms of Ang-(1-7)/Mas on a-syn pathology, but also throwed a new light upon miR-153-3p and NEAT1 as biomarkers and therapeutic targets in PD. Overall design: The right SNpc tissues of miRNA profiles in human a-syn (A53T) overexpressing mice  and human a-syn (A53T) overexpressing mice  were treated with Ang-(1-7)