Nordihydroguaiaretic acid activates the antioxidant pathway Nrf2/HO-1 and protects cerebellar granule neurons against oxidative stress.

Because the etiopathology of neurodegenerative diseases is tightly connected with oxidative stress, there is an increasing need to find compounds that might elicit an antioxidant and neuroprotective response in neurons. We found that nordihydroguaiaretic acid (NDGA), a powerful antioxidant from Larrea tridentate, activates the antioxidant pathway Nrf2/heme oxygenase-1 (HO-1) in cerebellar granule neurons and protects them against H(2)O(2) or 3-nitropropionic acid-induced neurotoxicity. The role of HO-1 in this protective effect was made evident by using an HO inhibitor, tin-mesoporphyrin. Our study identifies NDGA as a new potential therapeutic tool to activate the Nrf2/HO-1 axis for protection against oxidative stress.