期刊
BRAIN RESEARCH
卷 1722, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.brainres.2019.146331
关键词
Parkinson's disease; microRNA-137; Oxidation resistance 1; Exosomes; Oxidative stress
Recently, it has been demonstrated that microRNA-137 (miR-137) plays a vital role in the induction of oxidative stress of neurons in Parkinson's disease (PD). Herein, the study aimed to investigate the effects of serum exosomal miR-137 on oxidative stress injury of neurons in PD. Microarray analysis was adopted to screen the PD-related differential expressed genes and predict the interaction between OXR1 and miR-137 in PD. It was found that OXR1 was down-regulated while miR-137 was up-regulated in PD. Additionally, miR-137 targeted OXR1 and negatively regulated its expression. Mouse and neuron models of PD were established to mimic the pathological changes, especially oxidative stress injury induced by PD. The significance of miR-137 and OXR1 in oxidative stress injury was investigated in neuron model of PD using gain- and loss-of-function approaches. The obtained data exhibited that inhibition of miR-137 or up-regulation of OXR1 ameliorated PD-induced oxidative stress injury, reduced pole-climbing time, but increased score for traction test as well as promoted viability and decreased apoptosis of neurons in PD model, accompanied with decreased MDA content and ROS levels, and increased SOD levels. Furthermore, PD mice were injected with serum-derived exosomes or neurons in PD models were exposed to exosomes derived from serum of PD mice. Loss-of-function experiments using miR-137 antagomir exhibited that inhibition of exosomal miR-137 ameliorated PD-induced oxidative stress injury in vitro, reduced pole-climbing time but increased score for traction test in vivo. Collectively, down-regulation of exosomal miR-137 alleviates oxidative stress injury in PD by up-regulating OXR1.
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