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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.