Cannabidiol Induces Autophagy to Protects Neural Cells From Mitochondrial Dysfunction by Upregulating SIRT1 to Inhibits NF-κB and NOTCH Pathways.

Shaolei Kang,Jinglin Li,Zhihui Yao,Jiaxin Liu

doi:10.3389/fncel.2021.654340

Abstract

The protective effect of Cannabidiol on Parkinson’s disease (PD) has been found in recent study. However, the specific mechanism of the protective effect of Cannabidiol on PD nerve damage require further exploration. This study aims to investigate effect of Cannabidiol on MMP-induced Neural Cells (SH-SY5Y) mitochondrial dysfunction. MMP+ and Cannabidiol were used to treat SH-SY5Y cells, the cells viability was measured by MTT assay. The expression of Tyrosine hydroxylase (TH) in cells was measured by western blotting and Immunofluorescence staining. The relationship among Cannabidiol, Silent mating type information regulation 2 homolog-1 (SIRT1) and NOTCH signaling, NF-κB signaling was examined by western blotting. The effect of Cannabidiol on MMP+-induced mitochondrial dysfunction of SH-SY5Y cells was measured by western blotting. Cannabidiol alleviated loss of TH expression and cytotoxicity in the MPP+-induced SH-SY5Y cells. Further mechanistic investigation showed that Cannabidiol induced SH-SY5Y cells autophagy to protects cells from mitochondrial dysfunction by upregulating SIRT1 to Inhibits NF-κB and NOTCH Pathways. Taken together, Cannabidiol acts as a protector in PD.

Highlights

Parkinson’s disease (PD) is a common neurodegenerative disease (Jasmin et al, 2020)
The results of western blotting showed that si-SITR1 transfected and 3MA treatmented decreased the expression of LC3-II, Atg5/7 and Nrf2, SOD-1, GSH, enhanced the expression p62, α-synuclein, compared with the pretreatment of cells with Cannabidiol alone (Figures 4C,D). This data indicates that blockade of autophagy and knockdown of Silent mating type information regulation homolog-1 (SIRT1) attenuated the alleviation effect of Cannabidiol on the dysfunction of mitochondrial induced by MPP+
We provide evidence that Cannabidiol attenuated the loss of Tyrosine hydroxylase (TH) and the accumulation of α-synuclein expression, simultaneously restored the levels of antioxidant protein and autophagy protein in SH-SY5Y cells induced by MPP+

Summary

Introduction

Parkinson’s disease (PD) is a common neurodegenerative disease (Jasmin et al, 2020). More than 6 million individuals suffering from PD globally, which seriously endangers human health in their lives (Nobre et al, 2020). The characteristics of PD include the gradual loss of dopaminergic neurons in substantial nigra pars compacta and the abnormal accumulation of α-synuclein, which further leads to motor dysfunction (Sveinbjornsdottir, 2016; Opara et al, 2017). The common treatment for PD is the administration of a dopamine precursor to relieve the clinical symptoms of PD patients (Santiago et al, 2017). Cannabidiol Alleviate Parkinson’s Development drugs or method to restore and prevent neuronal damage. The development of new adjuvant therapies and therapeutic targets is crucial

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