A Novel Compound ITC-3 Activates the Nrf2 Signaling and Provides Neuroprotection in Parkinson’s Disease Models

Title
A Novel Compound ITC-3 Activates the Nrf2 Signaling and Provides Neuroprotection in Parkinson’s Disease Models
Authors
이재애손효진박기덕한세희신나리김지현김혜리김동진황온유
Keywords
Parkinson's disease; Substantia nigra; Neuroinflammation; Oxidative stress; Neuroprotection
Issue Date
2015-11
Publisher
NEUROTOXICITY RESEARCH
Citation
VOL 28, NO 4, 332-345
Abstract
Parkinson's disease (PD) is a progressive neurodegenerative disorder accompanied by a selective loss of the dopamine(DA)ergic neurons residing in the substantia nigra. There is ample evidence that neuroinflammation and oxidative stress are involved in the pathogenesis of PD. In the present study, we aimed at protecting the DAergic neurons by suppressing these cellular events and generated a novel synthetic isothiocyanate ITC-3. The compound led to elevation of nuclear and total levels of the transcription factor Nrf2 and interacted with its binding protein Keap1 with high affinity, suggesting Nrf2 activation. ITC-3 was able to suppress production of the proinflammatory mediators in lipopolysaccharide-activated BV-2 microglial cells. It also increased mRNA and protein levels of the Nrf2-dependent antioxidant enzymes NAD(P)H quinone oxidoreductase, heme oxygenase-1, and glutamylcysteine ligase in both BV-2 and DAergic neuronal CATH.a cells. The compound protected the DAergic cells against oxidative stress. In vivo, ITC-3 attenuated the loss of tyrosine hydroxylase-immunopositive nigrostriatal DAergic neurons, suppressed microglial activation, and abolished PD-associated motor deficits in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-elicited animal model of PD. Taken together, ITC-3 may be useful toward development of neuroprotective therapy for PD.
URI
http://pubs.kist.re.kr/handle/201004/50663
ISSN
10298428
Appears in Collections:
KIST Publication > Article
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