AVE0991 ameliorates dopaminergic neuronal damage in Parkinson's disease through HOTAIRM1/miR-223-3p/α-synuclein axis.

Autor: Duan R; Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.; Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China., Shi L; Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China., Deng Y; School of Basic Medicine & Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211198, China., Wu J; Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China., Wang S; Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China., Peng Q; Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China., Li Z; Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China., Xu Z; Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China., Wang F; Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China. fengwangcn@hotmail.com., Xue X; Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China. luoboxue1987@163.com., Gao Q; Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China. gaoqing19890205@163.com.; Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China. gaoqing19890205@163.com.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Nov 01; Vol. 14 (1), pp. 26346. Date of Electronic Publication: 2024 Nov 01.
DOI: 10.1038/s41598-024-76058-w
Abstrakt: Parkinson's disease (PD) is a prevalent type of neurodegenerative disorder. 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 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 [ 18 F] FDG-PET/CT method was employed to assess FDG uptake in human α-syn (A53T) overexpressing mice. Levels of lnc HOTAIRM1 and miR-223-3p were detected via qRT-PCR. Flow cytometry was deployed to assay cell apoptosis. Here, we found that AVE0991 improved behaviour disorders and decreased α-syn expression in the substantia nigra of mice with Parkinson's disease. AVE0991 inhibited the apoptosis of dopaminergic neurons overexpressing hα-syn (A53T) via lncRNA HOTAIRM1. MiR-223-3p binds to HOTAIRM1 as a ceRNA and directly targets α-syn. Moreover, miR-223-3p level in peripheral blood was found negatively correlated with the 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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