Neuroprotection of Indole-Derivative Compound NC001-8 by the Regulation of the NRF2 Pathway in Parkinson's Disease Cell Models

Pei Cih Wei, Guey Jen Lee-Chen, Chiung Mei Chen, Yih Ru Wu, Yi Jing Chen, Jia Li Lin, Yen Shi Lo, Ching Fa Yao, Kuo Hsuan Chang*

*此作品的通信作者

研究成果: 雜誌貢獻期刊論文同行評審

19 引文 斯高帕斯(Scopus)

摘要

Parkinson's disease (PD) is a common neurodegenerative disease accompanied by a loss of dopaminergic (DAergic) neurons. The development of therapies to prevent disease progression is the main goal of drug discovery. There is increasing evidence that oxidative stress and antioxidants may contribute to the pathogenesis and treatment of PD, respectively. In the present study, we investigated the antioxidative protective effects of the indole-derivative compound NC001-8 in DAergic neurons derived from SH-SY5Y cells and PD-specific induced pluripotent stem cells (PD-iPSCs) carrying a PARKIN ex5del mutation. In SH-SY5Y-differentiated DAergic neurons under 1-methyl-4-phenylpyridinium (MPP+) treatment, NC001-8 remarkably reduced the levels of reactive oxygen species (ROS) and cleaved caspase 3; upregulated nuclear factor erythroid 2-related factor 2 (NRF2) and NAD(P)H dehydrogenase, quinone 1 (NQO1); and promoted neuronal viability. In contrast, NRF2 knockdown abolished the effect of NC001-8 on the reduction of ROS and improvement of neuronal viability. In H2O2-treated DAergic neurons differentiated from PD-iPSCs, NC001-8 rescued the aberrant increase in ROS and cleaved caspase 3 by upregulating NRF2 and NQO1. Our results demonstrated the protective effect of NC001-8 in DAergic neurons via promoting the NRF2 antioxidative pathway and reducing ROS levels. We anticipate that our present in vitro assays may be a starting point for more sophisticated in vivo models or clinical trials that evaluate the potential of NC001-8 as a disease modifier for PD.

原文英語
文章編號5074367
期刊Oxidative medicine and cellular longevity
2019
DOIs
出版狀態已發佈 - 2019

ASJC Scopus subject areas

  • 生物化學
  • 老化
  • 細胞生物學

指紋

深入研究「Neuroprotection of Indole-Derivative Compound NC001-8 by the Regulation of the NRF2 Pathway in Parkinson's Disease Cell Models」主題。共同形成了獨特的指紋。

引用此