Long noncoding RNA GAS5 promotes microglial inflammatory response in Parkinson's disease by regulating NLRP3 pathway through sponging miR-223-3p

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Neuroinflammation induced by microglia plays an important role in the pathogenesis of PD. Long noncoding RNA GAS5 was showed to have significant effects on regulating inflammatory response. Here, we aim to investigate the effects of GAS5 on the inflammatory response of PD, and the underlying mechanism. An in vivo model of PD was established in C57BL/6 mice by rotenone and an in vitro cell model was conducted on microglia by lipopolysaccharide (LPS). Our results indicated that GAS5 was upregulated in tissues in a mice model of PD and microglia activated by LPS. Gain- and loss- of functional experiments demonstrated that GAS5 promoted the inflammation of microglia in vitro. Besides, the knockdown of GAS5 repressed the PD progression in vivo. Mechanistically, GAS5 positively regulated the NLRP3 expression via competitively sponging miR-223-3p. Overall, our finding illuminates that GAS5 accelerates PD progression through targeting miR-223-3p/NLRP3 axis.

Keywords: GAS5; Inflammation; NLRP3; Parkinson’s disease; miR-223-3p.