miR-100a-5p-enriched exosomes derived from mesenchymal stem cells enhance the anti-oxidant effect in a Parkinson's disease model via regulation of Nox4/ROS/Nrf2 signaling

作者：He, Songzhe; Wang, Qiongqiong; Chen, Liankuai; He, Yusheng Jason; Wang, Xiaofang; Qu, Shaogang^*

来源：Journal of Translational Medicine, 2023, 21(1): 747.

DOI：10.1186/s12967-023-04638-x

• Parkinson's disease
• Dopaminergic neuron
• Mesenchymal stem cell
• Exosomes
• miR-100-5p
• NOX4

Background The pathogenesis of Parkinson's disease (PD) has not been fully elucidated, and there are no effective disease-modifying drugs for the treatment of PD. Mesenchymal stem cells have been used to treat several diseases, but are not readily available. @@@ Methods Here, we used phenotypically uniform trophoblast stage-derived mesenchymal stem cells (T-MSCs) from embryonic stem cells, which are capable of stable production, and their exosomes (T-MSCs-Exo) to explore the molecular mechanisms involved in dopaminergic (DA) neuron protection in PD models using experimental assays (e.g., western blotting, immunofluorescence and immunohistochemistry staining). @@@ Results We assessed the levels of DA neuron injury and oxidative stress in MPTP-induced PD mice and MPP+- induced MN9D cells after treating them with T-MSCs or T-MSCs-Exo. Furthermore, T-MSCs-Exo miRNA sequencing analysis revealed that miR-100-5p-enriched T-MSCs-Exo directly targeted the 3' UTR of NOX4, which could protect against the loss of DA neurons, maintain nigro-striatal system function, ameliorate motor deficits, and reduce oxidative stress via the Nox4-ROS-Nrf2 axis in PD models. @@@ Conclusions The study suggests that miR-100-5p-enriched T-MSCs-Exo may be a promising biological agent for the treatment of PD.

• 单位
  南方医科大学