MicroRNA-326 Inhibits Apoptosis and Promotes Proliferation of Dopaminergic Neurons in Parkinson ’s Disease Through Suppression of KLK7-Mediated MAPK Signaling Pathway

AbstractParkinson ’s disease (PD), one of the motor system disorders, is characterized by the loss of dopamine-producing brain cells. Accumulating evidence has highlighted the involvement of microRNAs (miRs) in the development and progression of PD. Hence, we aimed at exploring possible effects of miR-326 on the pr ogression of PD in mice in an attempt to elucidate the underlying mechanism associated with the kallikrein-related peptidase 7 (KLK7)–mediated mitogen-activated protein kinase (MAPK) signaling pathway. In order to identify the regulatory relationship between miR-326 and KLK7 and its biological sig nificance in PD, PD mouse models were established and subsequently treated with mimics or inhibitors of miR-326 or siRNA-KLK7. The content of striatal dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxytyrosine (3-MT), superoxide dismutase (SOD), glutathione per oxidase (GSH-Px), and malondialdehyde (MDA); positive expression of tyrosine hydroxylase (TH) and inducible nitric oxide synthase (iNOS); and the levels of IL-1, IL-6, TNF-α, INF- γ, and MAPK signaling pathway–related genes were determined accordingly. The results obtained indicated that KLK7 was negatively targeted by miR-326, with lower miR-326 and higher KLK7 detected among PD mice. The overexpression of miR-326 or silencing of KLK7 was demonstrated to increase the cont ent of DA, DOPAC, HVA, 3-MT, SOD, GSH-Px, and TH positive expression, while reducing iNOS positiv...
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research