Corynoxine Protects Dopaminergic Neurons Through Inducing Autophagy and Diminishing Neuroinflammation in Rotenone-Induced Animal Models of Parkinson's Disease.

Leilei Chen,Youcui Wang,Yingyu Huang,Junxia Xie,Jiahong Lu,Liangfeng Liu,Wenting Jia,Min Li,Xing Yu,Juxian Song,Yujv Huang

doi:10.3389/fphar.2021.642900

Abstract

Recent studies have shown that impairment of autophagy is related to the pathogenesis of Parkinson’s disease (PD), and small molecular autophagy enhancers are suggested to be potential drug candidates against PD. Previous studies identified corynoxine (Cory), an oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla (Miq.) Jacks, as a new autophagy enhancer that promoted the degradation of α-synuclein in a PD cell model. In this study, two different rotenone-induced animal models of PD, one involving the systemic administration of rotenone at a low dosage in mice and the other involving the infusion of rotenone stereotaxically into the substantia nigra pars compacta (SNpc) of rats, were employed to evaluate the neuroprotective effects of Cory. Cory was shown to exhibit neuroprotective effects in the two rotenone-induced models of PD by improving motor dysfunction, preventing tyrosine hydroxylase (TH)-positive neuronal loss, decreasing α-synuclein aggregates through the mechanistic target of the rapamycin (mTOR) pathway, and diminishing neuroinflammation. These results provide preclinical experimental evidence supporting the development of Cory into a potential delivery system for the treatment of PD.

Highlights

Parkinson’s disease (PD) is the second most common neurodegenerative disease, affecting more than 1% of the population over the age of 60 years
A previous study conducted by our research group identified corynoxine (Cory), an indole alkaloid isolated from the Chinese herb Uncaria rhynchophylla (Chen et al, 2014; Chen et al, 2017), as a new autophagy enhancer that promoted the clearance of α-synuclein in a cell model of PD
In the year 2000, rotenone was first reported to show features of PD following chronic systemic exposure (Betarbet et al, 2000). These effects were reported to be similar to those produced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and since animal models induced by rotenone have been investigated

Summary

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disease, affecting more than 1% of the population over the age of 60 years. In 2005, it was predicted that the number of individuals (age > 50 years) with PD would double by 2030, and this number increased by approximately 10% in 2018 (Rossi et al, 2018) Both selective degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the appearance of Lewy bodies, whose main component is aggregated α-synuclein, in the remaining neurons are thought to be the major pathological. A previous study conducted by our research group identified corynoxine (Cory), an indole alkaloid isolated from the Chinese herb Uncaria rhynchophylla (Chen et al, 2014; Chen et al, 2017), as a new autophagy enhancer that promoted the clearance of α-synuclein in a cell model of PD. It is necessary to evaluate the neuroprotective properties of Cory in animal models of PD prior to commencing clinical trials

Methods

Results

Conclusion