alpha-cyclodextrin/Moringin induces an antioxidant transcriptional response activating Nrf2 in differentiated NSC-34 motor neurons

Oxidative stress is a common feature of neurodegenerative diseases. Different natural compounds mediate neuroprotective effects activating Nrf2 antioxidant response. Some isothiocy-anates are Nrf2 activators, including moringin (MOR). In this study, the transcriptional profile of differentiated NSC-34 motor neurons was evaluated after the treatment for 48h and 96h with the concentrations 0.5, 5 and 10 microM of a new MOR formulation obtained with alpha-cyclodextrin (alpha-CD). All the concentrations increased gene expression and nuclear levels of Nrf2 at 96h. However, the highest dose increased Nrf2 levels also at 48h. Then, Nrf2 interactors were selected using String and common biological processes (BP) between the groups were evaluated. alpha-CD/MOR was able to modulate BP related to response to oxidative stress, proteostasis and autophagy. Specifically, the treatment with 10 microM of alpha-CD/MOR for 96h induced glutathione synthesis and proteasome genes and reduced the expression of genes related to endoplasmic reticulum stress. Moreover, cleaved caspase 3 levels indicated no apoptosis in this group. These results indicate the beneficial effects of the prolonged alpha-CD/MOR supplementation, that are mediated, at least in part, by Nrf2 activation. Then, alpha-CD/MOR could be a valuable treatment against neurodegenerative disease, and in particular motor neuron degeneration