Journal
MOLECULAR NUTRITION & FOOD RESEARCH
Volume 54, Issue 4, Pages 532-542Publisher
WILEY
DOI: 10.1002/mnfr.200900197
Keywords
Antioxidant response element; Neurodegeneration; Parkinson's disease; Sulforaphane; 5-S-Cysteinyl-dopamine
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Funding
- Biotechnology and Biological Sciences Research Council [BB/C518222/1, BB/F008953/1, BB/G005702/1]
- Medical Research Council [G0400278]
- MIURCOFIN 2007 Italy
- BBSRC [BB/G005702/1, BB/F008953/1] Funding Source: UKRI
- MRC [G0400278] Funding Source: UKRI
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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 mu M) 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 lcinase 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.
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