Neuroprotective effects of protocatechuic aldehyde through PLK2/p-GSK3β/Nrf2 signaling pathway in both in vivo and in vitro models of Parkinson's disease.

Chao Guo,Aidong Wen,Jingwen Wang,Junrong Zhu,Yingdong Zhang,Wei Zhang,Wei Quan,Yi Ding,Jialin Duan,Ying Yin,Yue Guan,Shanbo Ma

doi:10.18632/aging.102394

Abstract

Mitochondrial dysfunction and oxidative damage are closely related to the pathogenesis of Parkinson's disease (PD). The pharmacological mechanism of protocatechuic aldehyde (PCA) for PD treatment have retained unclear. The purposes of the present study were to clarify the neuroprotective effects of post-treatment of PCA for PD treatment by mitigating mitochondrial dysfunction and oxidative damage, and to further determine whether its effects were mediated by the polo-like kinase 2/phosphorylated glycogen synthase kinase 3 β/nuclear factor erythroid-2-related factor 2 (PLK2/p-GSK3β/Nrf2) pathways. We found that PCA improved 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced behavioral deficits and dopaminergic cell loss. Moreover, PCA increased the expressions of PLK2, p-GSK3β and Nrf2, following the decrease of α-synuclein (α-Syn) in MPTP-intoxicated mice. Cell viability was increased and the apoptosis rate was reduced by PCA in 1-methyl-4-phenylpyridinium iodide (MPP+)-incubated cells. Mitochondrial membrane potential (MMP), mitochondrial complex I activity and reactive oxygen species (ROS) levels in MPP+-incubated cells were also ameliorated by treatment with PCA. The neuroprotective effects of PCA were abolished by inhibition or knockdown of PLK2, whereas overexpression of PLK2 strengthened the protection of PCA. Furthermore, GSK3β and Nrf2 were involved in PCA-induced protection. These results indicated that PCA has therapeutic effects on PD by the PLK2/p-GSK3β/Nrf2 pathway.

Highlights

Parkinson's disease (PD) is one of the most common neurodegenerative diseases, affecting approximately 2% of the world's population over 60 years of age [1]
These results suggested that post-treatment with protocatechuic aldehyde (PCA) could effectively improve the behavioral deficits in the mouse model of PD
Previous studies have shown that the MPTP-induced mice were orally pretreated with PCA for 14 days to protect against Parkinson’s disease [24], the present studies further certified that post-treatment of PCA can exert significant neuroprotection in MPTP-induced mice by intraperitoneal injection for 5 days

Summary

Introduction

Parkinson's disease (PD) is one of the most common neurodegenerative diseases, affecting approximately 2% of the world's population over 60 years of age [1]. The pathological feature of PD is the progressive degeneration of dopaminergic neurons in the substantia nigra (SN), resulting in a deficiency of dopamine (DA) in the striatum [2]. Drugs in clinical use, including levodopa, catechol-O-methyltransferase inhibitors, monoamine oxidase type B www.aging-us.com inhibitors, and serotonin agonists, mainly improve the symptoms by supplementing the lack of dopamine, but do not delay disease progression [3]. The long-term usage of levodopa produces side-effects like motor fluctuations and dyskinesias [4]. There is still an urgent need to develop an anti-PD agent which could alleviate PD symptoms, and produce neuroprotective effects

Methods

Results

Conclusion