Circular RNA circDLGAP4 exerts neuroprotective effects via modulating miR-134-5p/CREB pathway in Parkinson’s disease

Abstract Parkinson’s disease (PD) is a neurodegenerative disease which is characterized by the substantia nigra dopaminergic neurons denatured. Circular RNA (circRNA) DLGAP4 (circDLGAP4) was found to have neuroprotective effect. In this study, we aimed to investigate whether circDLGAP4 participates in the progression of PD. Here, our results showed that circDLGAP4 expression was decreased in MPTP-induced PD mouse model and MPP+-induced PD cell models. In vitro study revealed that circDLGAP4 could promote viability, reduce apoptosis, decrease mitochondrial damage, enhance autophagy and thereby attenuated the neurotoxic effects of MPP+ in SH-SY5Y and MN9D cells. Further research suggested that circDLGAP4 exerted its functions via regulating miR-134-5p. Moreover, we demonstrated that CREB was a target of miR-134-5p and CREB expression could be regulated by circDLGAP4/miR-134-5p axis. CircDLGAP4/miR-134-5p could also modulate the activation of CREB signaling and thereby influence the expression of CREB target genes including BDNF, Bcl-2 and PGC-1α in SH-SY5Y and MN9D cells. In all, our study identifies that circDLGAP4 exerts neuroprotective effects via modulating miR-134-5p/CREB pathway both in human and mouse.