Dataset Information
The Neuroprotective Effect of Dimethyl Fumarate in an MPTP-Mouse Model of Parkinson's Disease: Involvement of Reactive Oxygen Species/Nuclear Factor-?B/Nuclear Transcription Factor Related to NF-E2.
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ABSTRACT: Aim
Oxidative stress plays a key role in Parkinson disease (PD), and nuclear transcription factor related to NF-E2 (Nrf-2) is involved in neuroprotection against PD. The aim of the present study was to investigate a role for nuclear factor-?B (NF-?B)/Nrf-2 in the neurotherapeutic action of dimethyl fumarate (DMF) in a mouse model of PD and in vitro in SHSY-5Y cells.Results
Daily oral gavage of DMF (10, 30, and 100?mg/kg) significantly reduced neuronal cell degeneration of the dopaminergic tract and behavioral impairments induced by four injections of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Moreover, treatment with DMF prevented dopamine depletion, increased tyrosine hydroxylase and dopamine transporter activities, and also reduced the number of ?-synuclein-positive neurons. Furthermore, DMF treatment upregulated the Nrf-2 pathway, increased NeuN+/Nrf-2+ cell number in the striatum, induced activation of manganese superoxide dismutase and heme oxygenase-1, and regulated glutathione levels. Moreover, DMF reduced interleukin 1 levels, cyclooxygenase 2 activity, and nitrotyrosine neuronal nitrite oxide synthase expression. This treatment also modulated microglia activation, restored nerve growth factor levels, and preserved microtubule-associated protein 2 alterations. The protective effects of DMF treatment, via Nrf-2, were confirmed in in vitro studies, through inhibition of Nrf-2 by trigonelline.Innovation
These findings demonstrate that DMF, both in a mouse model of PD and in vitro, provides, via regulation of the NF-?B/Nrf-2 pathway, novel cytoprotective modalities that further augment the natural antioxidant response in neurodegenerative and inflammatory disease models.Conclusion
These results support the thesis that DMF may constitute a promising therapeutic target for the treatment of PD. Antioxid. Redox Signal. 27, 453-471.
SUBMITTER: Campolo M
PROVIDER: S-EPMC5564046 | biostudies-literature | 2017 Sep
REPOSITORIES: biostudies-literature
Publications
The Neuroprotective Effect of Dimethyl Fumarate in an MPTP-Mouse Model of Parkinson's Disease: Involvement of Reactive Oxygen Species/Nuclear Factor-κB/Nuclear Transcription Factor Related to NF-E2.
Antioxidants & redox signaling 20170127 8
<h4>Aim</h4>Oxidative stress plays a key role in Parkinson disease (PD), and nuclear transcription factor related to NF-E2 (Nrf-2) is involved in neuroprotection against PD. The aim of the present study was to investigate a role for nuclear factor-κB (NF-κB)/Nrf-2 in the neurotherapeutic action of dimethyl fumarate (DMF) in a mouse model of PD and in vitro in SHSY-5Y cells.<h4>Results</h4>Daily oral gavage of DMF (10, 30, and 100 mg/kg) significantly reduced neuronal cell degeneration of the dop ...[more]
