[No authors listed]
Parkinson's disease (PD) is a common progressive neurodegenerative disorder occurring in older individuals. Mechanistically, neuroinflammation is a central pathological change in the progression of PD. Activation of microglia is widely considered to be a major trigger for neuroinflammation. Certain microRNAs (miRs) are key factors in inhibiting or stimulating inflammation during the occurrence and development of PD, among which miRâ195 may be a potential crucial biomarker. However, the underlying pathological mechanisms remain unclear. To investigate the pathogenesis of PD, lipopolysaccharide (LPS) was used to establish an in vitro model of microglia activation in the present study. It was revealed that miRâ195 expression was decreased in LPSâstimulated BV2 cells, suggesting a potential mechanism of action of miRâ195 on microglia activation. Furthermore, gainâ and lossâofâfunction experiments were performed by successful transfection of microglia with miRâ195 mimics or inhibitors. The results demonstrated that miRâ195 overexpression inhibited the release of proâinflammatory cytokines, including inducible nitric oxide synthase, interleukinâ6 (ILâ6) and tumor necrosis factorâα, but induced the release of antiâinflammatory cytokines in LPSâtreated BV2 cells, including ILâ4 and ILâ10. In addition, Rhoâassociated kinase 1 (ROCK1), which is negatively regulated by miRâ195, was increased in LPSâstimulated BV2 cells. ROCK1 knockdown with small interfering RNA exhibited the same effect as miRâ195 overexpression on regulating microglia status, suggesting that the miRâ195/ROCK1 interaction serves a central role in inducing microglia activation. Furthermore, inhibition of ROCK1 impaired cell viability and proliferation but induced cell apoptosis in LPSâtreated miRâ195âdeficient BV2 cells. The present results suggest that miRâ195 is a potential therapeutic target for PD.
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