AVE0991, hu-man alfa- sin'deki (A53T) dopaminerjik nöronları korumak ve davranışları iyileştirmek için HOTAIRM1/miR-223-3p/alfa-sinüklein'i düzenler.

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Abstract Parkinson's disease (PD) is a prevalent type of neurodegenerative disorders. 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 re-mains unclear. The mice overexpressing of human α-syn (A53T) were established to simulate PD pathology, and we also constructed an in vitro model of mouse dopaminergic neurons overexpressing hα-syn (A53T). The [18F] FDG-PET/CT method was also employed to assess FDG uptake in human α-syn (A53T) overexpressing mice. Levels of lnc HOTAIRM1, miR-223-3p were detected via qRT-PCR. Flow cytometry was deployed to assay cell apoptosis. Here, we found that AVE0991 improved behaviour disorder and decreased α-syn expression in the substantia nigra in mice with Parkinson's disease. AVE0991 inhibited apoptosis of dopaminergic neurons overexpressing hα-syn (A53T) by lncRNA HOTAIRM1. MiR-223-3p binds to HOTAIRM1 as a ceRNA and directly targets α-syn. Our present study shows that the angiotensin-(1–7) analogue AVE0991 targeted at the HOTAIRM1/miR-223-3p axis to degrade α-synuclein in PD mice, and showed neuroprotection in vitro.

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