Long Noncoding RNA SNHG1 Promotes Neuroinflammation in Parkinson's Disease via Regulating miR-7/NLRP3 Pathway

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorders. Neuroinflammation plays an important role in the pathogenesis of PD. Long noncoding RNA small nucleolar RNA host gene 1 (SNHG1) was elevated in the brain specimens of PD patients and MPP+-treated SH-SY5Y cells. The expression of mouse Snhg1 and miR-7 was firstly determined in lipopolysaccharide (LPS)-induced BV2 cells. The role and mechanism of SNHG1 in the neuroinflammation of PD were investigated using gain- and loss-of function approaches both in vitro and in vivo. Snhg1 expression was elevated, whereas miR-7 reduced in LPS-induced BV2 cells. Upregulation of Snhg1 elevated, and Snhg1 knockdown suppressed LPS-induced BV2 microglial activation and inflammation. miR-7 reversed, while anti-miR-7 further enhanced the effects of Snhg1 on BV2 cells. Furthermore, we found that Snhg1 functioned as a competing endogenous RNA for miR-7 to regulate nod-like receptor protein 3 (NLRP3) expression, leading to the activation of NLRP3 inflammasome. In the microglial culture supernatant transfer model, knockdown of Snhg1 or NLRP3 in LPS-stimulated BV2 cells inhibited primary neurons from apoptosis and elevated caspase-3 activity. Additionally, Snhg1 was increased in MPTP-induced PD mouse models. Downregulation of Snhg1 elevated miR-7 expression, suppressed the activation of microglia and NLRP3 inflammasome as well as dopaminergic neuron loss in the midbrain substantia nigra pars compacta in MPTP-treated mice. In conclusion, our study suggests that SNHG1 promotes neuroinflammation in the pathogenesis of PD via modulating miR-7/NLRP3 pathway.

Keywords: NLRP3 inflammasome; Parkinson’s disease; long noncoding RNA SNHG1; miR-7; neuroinflammation.