TY - JOUR T1 - Mechanism of miR-132-3p Promoting Neuroinflammation and Dopaminergic Neurodegeneration in Parkinson’s Disease JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0393-21.2021 SP - ENEURO.0393-21.2021 AU - Xin Gong AU - Mengyi Huang AU - Lei Chen Y1 - 2022/01/03 UR - http://www.eneuro.org/content/early/2022/01/02/ENEURO.0393-21.2021.abstract N2 - The major pathology in Parkinson’s disease (PD) is neuron injury induced by degeneration of dopaminergic neurons and the activation of microglial cells. The objective of this study is to determine the effect and mechanism of miR-132-3p in regulating neuroinflammation and the degeneration of dopaminergic neuron in PD. The expressions of miR-132-3p in brain tissues of PD patients, lipopolysaccharide (LPS)-induced BV-2 cells and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models were detected. The effect of miR-132-3p and GLRX in cell viability, apoptosis and inflammation was verified in BV-2 cells. The activation of Iba1 in substantia nigra pars compacta (SNc) and the loss of tyrosine hydroxylase were detected in PD mouse models and the mobility of mouse models was assessed as well. The targeting relationship between miR-132-3p and GLRX was confirmed by RNA immunoprecipitation (RIP) and dual luciferase reporter gene assay. Elevated expression of miR-132-3p and decreased expression of GLRX were found in PD patients and cells models. Overexpression of miR-132-3p can induce activation of microglial cells, which can be reversed by GLRX overexpression. Collected evidence in both cell model and mouse models showed the effect of miR-132-3p in enhancing the activation of microglial cells and the loss of microglia cells, which was achieved by mediating GLRX.Significance StatementThe purpose of this study is to explore the possible effect and mechanism of miR-132-3p/GLRX on neuroinflammation and the degeneration of dopaminergic neuron in Parkinson’s disease (PD). This is important as no effective treatment is available to cure PD and better understanding on how neuroinflammation and degeneration of dopaminergic neurons was regulated in PD will facilitate the proposal of therapeutic strategy. Future study should further validate the role and mechanism of miR-132-3p in regulating PD through GLRX before miR-132-3p can be proposed as a novel therapeutic target. ER -