Lee, Ji Ae Son, Hyo Jin Kim, Ji Hyun Park, Ki Duk Shin, Nari Kim, Hye Ri Kim, Eun Mee Kim, Dong Jin Hwang, Onyou 2024-01-20T03:02:59Z 2024-01-20T03:02:59Z 2021-09-04 2016-11 1071-5762 https://pubs.kist.re.kr/handle/201004/123523 The degenerative process of the nigral dopamine(DA)rgic neurons in Parkinson's disease (PD) involves both oxidative stress and neuroinflammation. In the present study, we aimed at developing a novel antioxidant and anti-inflammatory agent for PD therapy. Toward this end, we screened a novel focused library of isothiocyanate derivatives that we have generated for an anti-inflammatory property. We obtained a novel compound ITC-57 and found that ITC-57 effectively induced gene expression of the antioxidant enzymes NAD(P)H quinone oxidoreductase-1, the catalytic and modulatory subunits of glutamylcysteine ligase, and HO-1 in DAergic neuronal CATH.a cells and protected CATH.a cells from oxidative damages. The compound also induced the same antioxidant enzymes in microglial BV-2 cells and suppressed the production of the proinflammatory molecules nitric oxide, interleukin-1 (IL-1) and tumor necrosis factor- (TNF-) in lipopolysaccharide-activated BV-2 cells. In the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-elicited mouse model of PD, ITC-57 protected the DAergic neurons from degeneration, induced HO-1, lowered TNF-, and suppressed microglial activation in the nigra. Furthermore, ITC-57 prevented the PD-associated motor deficits from occurring. Taken together, ITC-57 would be useful toward development of a disease-modifying therapy for PD. English TAYLOR & FRANCIS LTD HEME OXYGENASE-1 DOPAMINERGIC-NEURONS NEURODEGENERATIVE DISEASES GLUTATHIONE METABOLISM THERAPEUTIC TARGET SUBSTANTIA-NIGRA NEUROINFLAMMATION BRAIN TETRAHYDROBIOPTERIN ALPHA A novel synthetic isothiocyanate ITC-57 displays antioxidant, anti-inflammatory, and neuroprotective properties in a mouse Parkinson's disease model Article 10.1080/10715762.2016.1223293 1 FREE RADICAL RESEARCH, v.50, no.11, pp.1188 - 1199 FREE RADICAL RESEARCH 50 11 1188 1199 scie scopus 000390113700004 2-s2.0-84986184347 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article HEME OXYGENASE-1 DOPAMINERGIC-NEURONS NEURODEGENERATIVE DISEASES GLUTATHIONE METABOLISM THERAPEUTIC TARGET SUBSTANTIA-NIGRA NEUROINFLAMMATION BRAIN TETRAHYDROBIOPTERIN ALPHA Parkinson&apos s disease neuroinflammation oxidative stress neuroprotection