Background: Parkinson’s disease (PD) is a neurodegenerative disorder caused by the
progressive loss of dopaminergic neurons. Canopy fibroblast growth factor signaling regulator 2 (CNPY2)
is down-regulated in this disease, but its functions are unknown.
Objective: This study investigates the effects and regulation of CNPY2 in the apoptosis of neurons
Methods: We established a PD model in vivo by a five consecutive days-injection of 1-methyl-4-
phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to mice. In vitro, the human SH-SY5Y neuroblastoma
cells, after differentiation, were treated with 1-Methyl-4-phenylpyridinium iodide (MPP+) for modeling.
The cells were transfected with a recombinant vector overexpressing CNPY2 followed by
MPP+ treatment. Expression of CNPY2 and proteins related to apoptosis was detected by real-time
PCR, western blot, or immunofluorescence staining. The ROS level and mitochondrial membrane
potential were determined by flow cytometry. Cell viability and apoptosis were measured by MTT
assay and TUNEL staining.
Results: CNPY2 level was down-regulated both in the brain and retina of PD mice and also inhibited
in neurons by MPP+ in vitro. Overexpression of CNPY2 repressed the level of Bax and cleaved
caspase-3, enhanced Bcl-2 level, and promoted neurite length under MPP+ treatment. CNPY2 overexpression
reduced the accumulation of ROS and mitochondria dysfunction in neurons. The AKT/
GSK3β signaling pathway was activated by overexpressed CNPY2 to inhibit MPP+-induced neuronal
apoptosis, which was confirmed using an AKT inhibitor MK-2206 2HCl.
Conclusion: CNPY2 alleviates oxidative stress, mitochondria dysfunction, and apoptosis of neurons
induced by MPP+ by activating the AKT/ GSK3β signaling pathway.