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
✍ Scribed by David Vauzour; Maria Buonfiglio; Giulia Corona; Joselita Chirafisi; Katerina Vafeiadou; Cristina Angeloni; Silvana Hrelia; Patrizia Hrelia; Jeremy P. E. Spencer
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 394 KB
- Volume
- 54
- Category
- Article
- ISSN
- 1613-4125
No coin nor oath required. For personal study only.
✦ Synopsis
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.