Journal of cellular and molecular medicine
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Multiple mechanisms of dimethyl fumarate in amyloid β-induced neurotoxicity in human neuronal cells.
Alzheimer disease (AD) is characterized by a complex heterogeneity of pathological changes, and any therapeutic approach categorically requires a multi-targeted way. It has been demonstrated that together with the hallmarks of the disease such as neurofibrillary tangles and senile plaques, oxidative and inflammatory stress covered an important role. Dimethyl fumarate (DMF) is an orally bioavailable methyl ester of fumaric acid and activator of Nrf2 with potential neuroprotective and immunomodulating activities. ⋯ In both models, DMF pre-treatment (30 μM) preserved cellular viability from Aβ stimulation, reducing tau hyper-phosphorylation, much more efficiently then MMF (30 μM). Moreover, DMF was able to induce an activation of manganese superoxide dismutase (MnSOD) and heme-oxygenase-1 (HO-1), decreasing the severity of oxidative stress. Our results showed important multi-protective effects of DMF pre-treatment from Aβ stimulation both in in vitro and ex vivo models, highlighting an Nrf2/NF-κB-dependent mechanism, which could provide a valuable support to the therapies for neurodegenerative diseases today.