Neuroprotection of Indole-Derivative Compound NC001-8 by the Regulation of the NRF2 Pathway in Parkinson’s Disease Cell Models
Joint Authors
Chen, Chiung-Mei
Wu, Yih-Ru
Wei, Pei-Cih
Chen, Yi-Jing
Lin, Jia-Li
Lo, Yen-Shi
Yao, Ching-Fa
Lee-Chen, Guey-Jen
Chang, Kuo-Hsuan
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-10-31
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Wei, Pei-Cih& Lee-Chen, Guey-Jen& Chen, Chiung-Mei& Wu, Yih-Ru& Chen, Yi-Jing& Lin, Jia-Li…[et al.]. 2019. Neuroprotection of Indole-Derivative Compound NC001-8 by the Regulation of the NRF2 Pathway in Parkinson’s Disease Cell Models. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-15.
https://search.emarefa.net/detail/BIM-1203916
Modern Language Association (MLA)
Wei, Pei-Cih…[et al.]. Neuroprotection of Indole-Derivative Compound NC001-8 by the Regulation of the NRF2 Pathway in Parkinson’s Disease Cell Models. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-15.
https://search.emarefa.net/detail/BIM-1203916
American Medical Association (AMA)
Wei, Pei-Cih& Lee-Chen, Guey-Jen& Chen, Chiung-Mei& Wu, Yih-Ru& Chen, Yi-Jing& Lin, Jia-Li…[et al.]. Neuroprotection of Indole-Derivative Compound NC001-8 by the Regulation of the NRF2 Pathway in Parkinson’s Disease Cell Models. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-15.
https://search.emarefa.net/detail/BIM-1203916
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1203916