A novel synthetic isothiocyanate ITC-57 displays antioxidant, anti-inflammatory, and neuroprotective properties in a mouse Parkinson's disease model.
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-1β (IL-1β) and tumor necrosis factor-α (TNF-α) 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-α, 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.
a Department of Biochemistry and Molecular Biology , Cell Dysfunction Research Center (CDRC), University of Ulsan College of Medicine , Seoul, Korea.
Ji Ae
JA
Lee
a Department of Biochemistry and Molecular Biology , Cell Dysfunction Research Center (CDRC), University of Ulsan College of Medicine , Seoul, Korea.
Hyo Jin
HJ
Son
a Department of Biochemistry and Molecular Biology , Cell Dysfunction Research Center (CDRC), University of Ulsan College of Medicine , Seoul, Korea.
Ji Hyun
JH
Kim
b Center for Neuro-Medicine , Brain Science Institute, Korea Institute of Science and Technology , Seoul, Korea.
Ki Duk
KD
Park
a Department of Biochemistry and Molecular Biology , Cell Dysfunction Research Center (CDRC), University of Ulsan College of Medicine , Seoul, Korea.
Nari
N
Shin
a Department of Biochemistry and Molecular Biology , Cell Dysfunction Research Center (CDRC), University of Ulsan College of Medicine , Seoul, Korea.
Hye Ri
HR
Kim
c Department of Emergency Medical Technology , Korea Nazarene University , Cheonan , South Korea.
Eun Mee
EM
Kim
b Center for Neuro-Medicine , Brain Science Institute, Korea Institute of Science and Technology , Seoul, Korea.
Dong Jin
DJ
Kim
a Department of Biochemistry and Molecular Biology , Cell Dysfunction Research Center (CDRC), University of Ulsan College of Medicine , Seoul, Korea.
Onyou
O
Hwang
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D016923:Cell Death; D004195:Disease Models, Animal; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D017879:Isothiocyanates; D018696:Neuroprotective Agents
Parkinson’s disease; neuroinflammation; neuroprotection; oxidative stress