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

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

  • Sci Rep. 2024 Nov 1;14(1):26346. doi: 10.1038/s41598-024-76058-w.
Rui Duan # 1 2,  Liang Shi # 2,  Yang Deng # 3,  Jiang Wu 2,  Shiyao Wang 1,  Qiang Peng 1,  Zhongyuan Li 1,  Zhaohan Xu 1,  Feng Wang 4,  Xue Xue 5,  Qing Gao 6 7
Affiliations

Affiliations

  • 1 Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.
  • 2 Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.
  • 3 School of Basic Medicine & Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
  • 4 Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China. fengwangcn@hotmail.com.
  • 5 Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China. luoboxue1987@163.com.
  • 6 Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China. gaoqing19890205@163.com.
  • 7 Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China. gaoqing19890205@163.com.
  • # Contributed equally.
PMID: 39487232 DOI: 10.1038/s41598-024-76058-w
Abstract

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 [18F] 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.

Keywords

AVE0991; HOTAIRM1; Parkinson’s disease; miR-223-3p; α-syn.

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