Son, Hyo Jin Choi, Ji Hyun Lee, Ji Ae Kim, Dong Jin Shin, Kye Jung Hwang, Onyou 2024-01-20T07:02:10Z 2024-01-20T07:02:10Z 2021-09-04 2015-06 0895-8696 https://pubs.kist.re.kr/handle/201004/125412 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 H2O2. 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. English HUMANA PRESS INC DOPAMINERGIC-NEURONS OXIDATIVE STRESS SH-SY5Y CELLS NAD(P)H-QUINONE OXIDOREDUCTASE-1 CYCLOOXYGENASE-2 EXPRESSION PROTEASOMAL DEGRADATION NEUROBLASTOMA-CELLS QUINONE FORMATION POTENTIAL ROLE DT-DIAPHORASE Induction of NQO1 and Neuroprotection by a Novel Compound KMS04014 in Parkinson's Disease Models Article 10.1007/s12031-015-0516-7 1 JOURNAL OF MOLECULAR NEUROSCIENCE, v.56, no.2, pp.263 - 272 JOURNAL OF MOLECULAR NEUROSCIENCE 56 2 263 272 scie scopus 000355753800003 2-s2.0-84930480947 Biochemistry & Molecular Biology Neurosciences Biochemistry & Molecular Biology Neurosciences & Neurology Article DOPAMINERGIC-NEURONS OXIDATIVE STRESS SH-SY5Y CELLS NAD(P)H-QUINONE OXIDOREDUCTASE-1 CYCLOOXYGENASE-2 EXPRESSION PROTEASOMAL DEGRADATION NEUROBLASTOMA-CELLS QUINONE FORMATION POTENTIAL ROLE DT-DIAPHORASE Parkinson&apos s disease Substantia nigra KMS04014 NQO1 Neuroprotection