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

摘要: Parkinson's disease (PD) is a progressive neurodegenerative disorder accompanied by selective loss of the dopamine(DA)ergic neurons residing in substantia nigra. There ample evidence that neuroinflammation and oxidative stress are involved pathogenesis PD. In present study, we aimed at protecting DAergic suppressing these cellular events generated novel synthetic isothiocyanate ITC-3. The compound led to elevation nuclear total levels transcription factor Nrf2 interacted with its binding protein Keap1 high affinity, suggesting activation. ITC-3 was able suppress production proinflammatory mediators lipopolysaccharide-activated BV-2 microglial cells. It also increased mRNA Nrf2-dependent antioxidant enzymes NAD(P)H quinone oxidoreductase, heme oxygenase-1, glutamylcysteine ligase both neuronal CATH.a protected cells against stress. vivo, attenuated tyrosine hydroxylase-immunopositive nigrostriatal neurons, suppressed activation, abolished PD-associated motor deficits 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-elicited animal model Taken together, may be useful toward development neuroprotective therapy for