Discovery of Vinyl Sulfones as a Novel Class of Neuroprotective Agents toward Parkinson’s Disease Therapy
Citations Over TimeTop 10% of 2014 papers
Abstract
Although the etiology of Parkinson's disease (PD) remains elusive, recent studies suggest that oxidative stress contributes to the cascade leading to dopaminergic (DAergic) neurodegeneration. The Nrf2 signaling is the main pathway responsible for cellular defense system against oxidative stress. Nrf2 is a transcription factor that regulates environmental stress response by inducing expression of antioxidant enzyme genes. We have synthesized novel vinyl sulfone derivatives. They exhibited a broad range of activities in inducing HO-1, whose gene expression is under the control of Nrf2. Among them, compound 12g was confirmed to activate Nrf2 and induce expression of the Nrf2-dependent antioxidant enzymes NQO1, GCLC, GLCM, and HO-1, at both mRNA and protein levels in DAergic neuronal cells. This was accompanied by protection of DAergic neurons in both in vitro and MPTP-induced in vivo models of PD. In addition, compound 12g effectively resulted in attenuation of the PD-associated behavioral deficits in the mouse model.
Related Papers
- → A chemical neurotoxin, MPTP induces Parkinson's disease like phenotype, movement disorders and persistent loss of dopamine neurons in medaka fish(2009)49 cited
- → Expression of c-Jun in dopaminergic neurons of the substantia nigra in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice(1997)33 cited
- → Age-Dependent Susceptibility to MPTP Neurotoxicity in C57BL Mice: A Tyrosine Hydroxylase-Immunohistochemical Evaluation(2004)4 cited
- → Investigation of the Possible Dopaminergic Toxicity of 1‐Methyl‐3‐phenyl‐1,2,3,6‐tetrahydropyridine, an Isomer to the Neurotoxin MPTP(1991)
- → In Recent Issues(2007)