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Current Neurovascular Research

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ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

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Research Article

Canopy Fibroblast Growth Factor Signaling Regulator 2 (CNPY2) Inhibits Neuron Apoptosis in Parkinson’s Disease via the AKT/GSK3β Pathway

Author(s): Miao Chu, Huimiao Liu, Zhaohui Xiong, Chaojuan Ju, Lina Zhao, Kangning Li, Shiqi Tian and Ping Gu*

Volume 18, Issue 1, 2021

Published on: 29 June, 2021

Page: [102 - 112] Pages: 11

DOI: 10.2174/1567202618666210531141833

Price: $65

Abstract

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 in PD.

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.

Keywords: Parkinson's disease, CNPY2, SH-SY5Y, MPP+, apoptosis, oxidative stress, mitochondria, AKT/GSK3β pathway.

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