Stabilization of transcription factor Nrf2 by tBHQ prevents oxidative stress-induced amyloid β formation in NT2N neurons

Abstract

Alzheimer's disease (AD) a progressive neurodegenerative disorder of later life, is characterized by brain deposition of amyloid β-protein (Aβ) plaques, accumulation of intracellular neurofibrillatory tangles, synaptic loss and neuronal cell death. There is significant evidence that oxidative stress is a critical event in the pathogenesis of AD. In the present study Aβ formation was induced in NT2N neurons, one of the most appropriate cell line models in AD. Our results indicate that oxidative stress resulting from the treatment of H 2O 2/FeSO 4 and/or 4-hydroxy-2-noenal (HNE) can be inhibited in the presence of tBHQ, a known inducer of nuclear factor-erythroid 2 related factor 2 (Nrf2) in NT2N neurons and can therefore be used to elucidate the relationship between oxidative stress, Aβ formation and Nrf2. The role of Nrf2 was confirmed using retinoic acid as an inhibitor of Nrf2. It provides the first documentation that tBHQ not only protects the neurons against cell death but also decreases amyloid β formation. Moreover, the results indicate that oxidative stress fosters Aβ formation in NT2N neurons, creating a vicious neurodegenerative loop.