NDLI: Induction of NQO1 and Neuroprotection by a Novel Compound KMS04014 in Parkinson’s Disease Models

Content Provider	Springer Nature Link
Author	Son, Hyo Jin Choi, Ji Hyun Lee, Ji Ae Kim, Dong Jin Shin, Kye Jung Hwang, Onyou
Copyright Year	2015
Abstract	Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with a selective loss of the neurons containing dopamine (DA) in the substantia nigra pars compacta. Lines of evidence suggest that oxidative stress is a major factor contributing to the vulnerability of DA cells and that the enzyme NAD(P)H quinone oxidoreductase (NQO1) provides protection in these cells. In the present study, we report the synthesis of a novel compound KMS04014 and show that it induces NQO1 gene expression and protects DAergic neuronal cells in both cell culture and animal models of PD. In vitro, KMS04014 increased both mRNA and protein levels of NQO1 and induced nuclear translocation of Nrf2 in the DAergic neuronal cell line CATH.a. It also protected the cells against oxidative stress generated by tetrahydrobiopterin, 1-methyl-4-phenylpyridinium (MPP$^{+}$), and H$_{2}$O$_{2}$. In vivo, KMS04014 attenuated the loss of tyrosine hydroxylase-immunopositive DAergic neurons in the substantia nigra and reduced degeneration of the nigral neurons and striatal fibers in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, an animal model of PD. Taken together, KMS04014 may be utilized toward development of neuroprotective therapy for PD.
Starting Page	263
Ending Page	272
Page Count	10
File Format	PDF
ISSN	08958696
Journal	Journal of Molecular Neuroscience
Volume Number	56
Issue Number	2
e-ISSN	15591166
Language	English
Publisher	Springer US
Publisher Date	2015-02-22
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Parkinson’s disease Substantia nigra KMS04014 NQO1 Neuroprotection Neurosciences Neurochemistry Cell Biology Proteomics Neurology
Content Type	Text
Resource Type	Article
Subject	Medicine Cellular and Molecular Neuroscience

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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