AVE0991 regulates HOTAIRM1/miR-223-3p/a-synuclein to improve behaviour and protect dopaminergic neurons in human a-syn (A53T) overexpressing mice
Objective: Parkinson's disease (PD) is part of a common type of neurodegenerative disease. AVE0991, a non-peptide analogue of Ang-(1-7), by which the progression of PD has been discovered to be ameliorated, but the specific mechanism whereby AVE0991 modulates the progression of PD remains unclear. Materials and Methods: During the study, the mice overexpressing of human a-syn(A53T) were established to simulate PD pathology, and we also constructed an in vitro model of mouse dopaminergic neurons overexpressing ha-syn(A53T). The [18F] FDG-PET/CT method was also employed to assess FDG uptake in human a-syn(A53T) overexpressing mice. Level of Lnc HOTAIRM1, miR-223-3p were detected via RT-qPCR. Flow cytometry was deployed to assay cell apoptosis. Results: AVE0991 improved behavior disorder and decreased a-syn expression in the substantia nigra in mice with Parkinson's disease. AVE0991 inhibited apoptosis of dopaminergic neurons overexpressing ha-syn(A53T) by LncRNA HOTAIRM1. MiR-223-3p binds to HOTAIRM1 as a ceRNA and directly targets a-syn. Conclusion:  The angiotensin-(1–7) analogue AVE0991 targeted the HOTAIRM1/miR-223-3p axis to degrade a-synuclein in PD mice, and showed neuroprotection in vitro. Overall design: The right SNpc tissues of lncRNA profiles in human a-syn (A53T) overexpressing mice  and human a-syn (A53T) overexpressing mice  were treated with AVE0991