The regulatory mechanism of miR-543-3p on GLT-1 in a mouse model of Parkinson's disease.

Parkinson's disease (PD) features the degeneration and death of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) and the formation of Lewy bodies that contain alpha-synuclein (α-Syn). Among the numerous PD etiologies, glutamate excitotoxicity is a research hotspot, and glutamate transporters play key roles in this theory. It has been shown that the expression of glutamate transporter is regulated by microRNAs. In this study, we found that the expression and function of glutamate transporter type one (GLT-1) were significantly reduced and miR-543-3p was upregulated during the development of PD. Furthermore, our results indicated that GLT-1 plays an important role in the pathomechanism of PD. We found that miR-543-3p can suppress the expression and function of GLT-1 in MPP+-treated astrocytes and MPTP-treated mice. Inhibiting miR-543-3p is able to rescue the expression and function of GLT-1 and relieve dyskinesia in the PD model, which suggests that inhibiting miR-543-3p could serve as a potential therapeutic target for PD.