PMID- 31781339
OWN - NLM
STAT- MEDLINE
DCOM- 20200420
LR  - 20200420
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2019
DP  - 2019
TI  - Neuroprotection of Indole-Derivative Compound NC001-8 by the Regulation of the 
      NRF2 Pathway in Parkinson's Disease Cell Models.
PG  - 5074367
LID - 10.1155/2019/5074367 [doi]
LID - 5074367
AB  - 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 H(2)O(2)-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.
CI  - Copyright (c) 2019 Pei-Cih Wei et al.
FAU - Wei, Pei-Cih
AU  - Wei PC
AUID- ORCID: 0000-0001-9726-6849
AD  - Department of Neurology, Chang Gung Memorial Hospital-Linkou Medical Center, 
      Chang Gung University School of Medicine, Taoyuan, Taiwan.
FAU - Lee-Chen, Guey-Jen
AU  - Lee-Chen GJ
AUID- ORCID: 0000-0003-4818-9917
AD  - Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
FAU - Chen, Chiung-Mei
AU  - Chen CM
AUID- ORCID: 0000-0002-0769-0353
AD  - Department of Neurology, Chang Gung Memorial Hospital-Linkou Medical Center, 
      Chang Gung University School of Medicine, Taoyuan, Taiwan.
FAU - Wu, Yih-Ru
AU  - Wu YR
AUID- ORCID: 0000-0003-1191-2542
AD  - Department of Neurology, Chang Gung Memorial Hospital-Linkou Medical Center, 
      Chang Gung University School of Medicine, Taoyuan, Taiwan.
FAU - Chen, Yi-Jing
AU  - Chen YJ
AD  - Department of Neurology, Chang Gung Memorial Hospital-Linkou Medical Center, 
      Chang Gung University School of Medicine, Taoyuan, Taiwan.
FAU - Lin, Jia-Li
AU  - Lin JL
AD  - Department of Neurology, Chang Gung Memorial Hospital-Linkou Medical Center, 
      Chang Gung University School of Medicine, Taoyuan, Taiwan.
FAU - Lo, Yen-Shi
AU  - Lo YS
AD  - Department of Neurology, Chang Gung Memorial Hospital-Linkou Medical Center, 
      Chang Gung University School of Medicine, Taoyuan, Taiwan.
FAU - Yao, Ching-Fa
AU  - Yao CF
AUID- ORCID: 0000-0002-8692-5156
AD  - Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan.
FAU - Chang, Kuo-Hsuan
AU  - Chang KH
AUID- ORCID: 0000-0003-4972-9823
AD  - Department of Neurology, Chang Gung Memorial Hospital-Linkou Medical Center, 
      Chang Gung University School of Medicine, Taoyuan, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20191031
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (Indoles)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone))
RN  - EC 1.6.5.2 (NQO1 protein, human)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - R865A5OY8J (1-Methyl-4-phenylpyridinium)
SB  - IM
MH  - 1-Methyl-4-phenylpyridinium/toxicity
MH  - Caspase 3/genetics/metabolism
MH  - Cell Line, Tumor
MH  - Dopaminergic Neurons/*metabolism/pathology
MH  - Humans
MH  - Indoles/*pharmacology
MH  - Induced Pluripotent Stem Cells/metabolism/pathology
MH  - *Models, Neurological
MH  - NAD(P)H Dehydrogenase (Quinone)/genetics/metabolism
MH  - NF-E2-Related Factor 2/*biosynthesis/genetics
MH  - Neuroprotection/*drug effects
MH  - Parkinson Disease, Secondary/*drug therapy/genetics/pathology
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/*drug effects/genetics
MH  - Up-Regulation/drug effects
PMC - PMC6874971
COIS- The authors declare that they have no competing interests.
EDAT- 2019/11/30 06:00
MHDA- 2020/04/21 06:00
PMCR- 2019/10/31
CRDT- 2019/11/30 06:00
PHST- 2018/11/27 00:00 [received]
PHST- 2019/04/05 00:00 [revised]
PHST- 2019/07/10 00:00 [accepted]
PHST- 2019/11/30 06:00 [entrez]
PHST- 2019/11/30 06:00 [pubmed]
PHST- 2020/04/21 06:00 [medline]
PHST- 2019/10/31 00:00 [pmc-release]
AID - 10.1155/2019/5074367 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2019 Oct 31;2019:5074367. doi: 10.1155/2019/5074367. 
      eCollection 2019.