Sulforaphane protects cortical neurons against 5‐S‐cysteinyl‐dopamine‐induced toxicity through the activation of ERK1/2, Nrf‐2 and the upregulation of detoxification enzymes
- 7 April 2010
- journal article
- research article
- Published by Wiley in Molecular Nutrition & Food Research
- Vol. 54 (4), 532-542
- https://doi.org/10.1002/mnfr.200900197
Abstract
The degeneration of dopaminergic neurons in the substantia nigra has been linked to the formation of the endogenous neurotoxin 5-S-cysteinyl-dopamine. Sulforaphane (SFN), an isothiocyanate derived from the corresponding precursor glucosinolate found in cruciferous vegetables has been observed to exert a range of biological activities in various cell populations. In this study, we show that SFN protects primary cortical neurons against 5-S-cysteinyl-dopamine induced neuronal injury. Pre-treatment of cortical neurons with SFN (0.01–1 μM) resulted in protection against 5-S-cysteinyl-dopamine-induced neurotoxicity, which peaked at 100 nM. This protection was observed to be mediated by the ability of SFN to modulate the extracellular signal-regulated kinase 1 and 2 and the activation of Kelch-like ECH-associated protein 1/NF-E2-related factor-2 leading to the increased expression and activity of glutathione-S-transferase (M1, M3 and M5), glutathione reductase, thioredoxin reductase and NAD(P)H oxidoreductase 1. These data suggest that SFN stimulates the NF-E2-related factor-2 pathway of antioxidant gene expression in neurons and may protect against neuronal injury relevant to the aetiology of Parkinson's disease.Keywords
Funding Information
- Biotechnology and Biological Sciences Research Council (BB/C518222/1, BB/F008953/1, BB/G005702/1)
- Medical Research Council (G0400278)
- MIUR-COFIN 2007 (project ♯ AYMLF) Italy
- Biomedical Research Centre University of Dundee
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