Salidroside Protects Dopaminergic Neurons by Enhancing PINK1/Parkin-Mediated Mitophagy.

Ruru Li,Jianzong Chen

doi:10.1155/2019/9341018

Abstract

Parkinson's disease (PD) is a common neurodegenerative disease characterized by the degeneration of nigrostriatal dopaminergic (DA) neurons. Our previous studies have suggested that salidroside (Sal) might play neuroprotective effects against PD by preserving mitochondrial Complex I activity. However, the exact mechanism of the neuroprotective effect of Sal remains unclear. Growing evidence indicates that PINK1/Parkin-mediated mitophagy is involved in the development of PD. In this study, we investigated whether Sal exerts a neuroprotective effect by modulating PINK1/Parkin-mediated mitophagy. Results showed that Sal alleviated MPTP-induced motor deficits in pole test. Moreover, Sal diminished MPTP-induced degeneration of nigrostriatal DA neurons as evidenced by upregulated TH-positive neurons in the substantia nigra, increased DAT expression, and high dopamine and metabolite levels in the striatum. Furthermore, in comparison with the MPP+/MPTP group, Sal considerably increased the mitophagosome and mitophagy flux. Moreover, in comparison with the MPP+/MPTP group, Sal evidently enhanced the mitochondrial expression of PINK1 and Parkin, accompanied by an increase in the colocalization of mitochondria with Parkin. However, transfection of MN9D cells with PINK1 siRNA reversed Sal-induced activated mitophagy and cytoprotective effect. In conclusion, Sal may confer neuroprotective effects by enhancing PINK1/Parkin-mediated mitophagy in MPP+/MPTP-induced PD models.

Highlights

Parkinson’s disease (PD) is the most common movement disorder and the second most common neurodegenerative disease after Alzheimer’s disease [1]
Mitochondria colocalized with Parkin is a hallmark of PINK1/Parkin-mediated mitophagy, we examined the colocalization of Parkin and MitoTracker [26]
We demonstrated that Sal may play a neuroprotective effect by modulating PINK1/Parkin-mediated mitophagy as evidenced by the following: (1) Sal treatment ameliorated MPTP-induced behavioral impairment; (2) Sal treatment attenuated MPTP-induced DA neuron damage; (3) Sal treatment notably increased mitophagy; (4) Sal treatment activated the PINK1/Parkin pathway; and (5) silencing PINK1 inhibited Sal-induced mitophagy and cytoprotective effect

Summary

Introduction

Parkinson’s disease (PD) is the most common movement disorder and the second most common neurodegenerative disease after Alzheimer’s disease [1]. Mitochondrial homeostasis is important for maintaining cell metabolism and function. Mitophagy is a key protective mechanism that selectively removes damaged or excessive mitochondria selectively via autophagy to maintain mitochondrial homeostasis [6, 7]. An increasing number of evidences have underpinned the importance of mitophagy on the onset of PD [9,10,11]. The studies in Drosophila for the first time depicted the effect of PINK1 and Parkin on mitochondrial function [12]. PINK1 is constitutively imported into mitochondria and rapidly cleaved and degraded. The degradation of PINK1 after import is disrupted when mitochondria are damaged, leading to PINK1 accumulation on the outer mitochondrial membrane and the recruitment of Parkin

Methods

Results

Conclusion