Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.64 (
MPP
)
1,876
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Neuroprotection of Indole-Derivative Compound NC001-8 by the Regulation of the NRF2 Pathway in Parkinson's Disease Cell Models. 3178 39
