Sulforaphane protects primary cortical neurons against 5-S-cysteinyl-dopamine-induced neurotoxicity.

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 the present 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 (ERK1/2) and the activation of Keap1/Nrf2 leading to the increased expression and activity of glutathione-S-transferase (GST M1, M3 and M5), glutathione reductase, thioredoxin reductase and NAD(P)H oxidoreductase 1. These data suggest that SFN stimulates the Nrf2 pathway of antioxidant gene expression in neurons and may protect against neuronal injury relevant to the aetiology of the Parkinson disease.