Stabilization of transcription factor Nrf2 by tBHQ prevents oxidative stress-induced amyloid beta formation in NT2N neurons.
Alzheimer's disease (AD) a progressive neurodegenerative disorder of later life, is characterized by brain deposition of amyloid beta-protein (Abeta) 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 Abeta 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(2)O(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, Abeta 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 beta formation. Moreover, the results indicate that oxidative stress fosters Abeta formation in NT2N neurons, creating a vicious neurodegenerative loop.
Eftekharzadeh
Bahareh
B
Neuroscience Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran.
Maghsoudi
Nader
N
Khodagholi
Fariba
F
D000447:Aldehydes / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D004789:Enzyme Activation; D005296:Ferrous Compounds / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006873:Hydroquinones / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000473:pathology*; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress; D014212:Tretinoin / Q000378:metabolism
D000447:Aldehydes; D016229:Amyloid beta-Peptides; D000970:Antineoplastic Agents; D000975:Antioxidants; D015853:Cysteine Proteinase Inhibitors; D005296:Ferrous Compounds; D006873:Hydroquinones; D051267:NF-E2-Related Factor 2; D016877:Oxidants; C020748:ferrous sulfate; D014212:Tretinoin; D006861:Hydrogen Peroxide; C018855:2-tert-butylhydroquinone; D053148:Caspase 3; D005978:Glutathione; C027576:4-hydroxy-2-nonenal