Dimethyl fumarate ameliorates parkinsonian pathology by modulating autophagy and apoptosis via Nrf2-TIGAR-LAMP2/Cathepsin D axis

Dimethyl Fumarate Exerts a Neuroprotective Effect by Enhancing Mitophagy via the NRF2/BNIP3/PINK1 Axis in the MPP+ Iodide-Induced Parkinson’s Disease Mice Model

“…The membrane was blocked using 3% BSA for 1-2 h, followed by overnight incubation in the following primary antibodies at 4°C: Anti-NRF2 (Sigma Aldrich, 1 : 1000), Anti-BNIP3 (Sigma Aldrich, 1 : 1000), TH (Santa Cruz, 1 : 2500), β-actin (Santa Cruz, 1 : 1000), α-synuclein (Santa Cruz, 1 : 500), NRF1 (Santa Cruz, 1 : 2500), PINK1 (Santa Cruz, 1 : 500), PARKIN (Santa Cruz, 1 : 500), LC3 (CST, 1 : 1000), BECLIN-1 (Santa Cruz, 1 : 1000), BCL2 (Santa Cruz, 1 : 500). Then, blots were incubated with HRP-conjugated anti-mouse (CST) and anti-rabbit (Santa Cruz) secondary antibody (1 : 10000 dilution) before visualizing using ECL reagent through chemiluminescence [ 39 ]. The relative band densities were quantified by densitometry using Image J analyzing software (Image J 1.53 k, National Institute of Health, Bethesda, MD, USA).…”

“…The sections were incubated in TH primary antibody (Santa Cruz, 1 : 200 dilution using 1% BSA in PBST) overnight at 4°C followed incubation in Alexa Fluor 488 secondary antibody (Invitrogen, 1 : 2000 dilution using 1% BSA in PBST) for 2 h in the dark at room temperature. The sections were counterstained with fluoroshield DAPI and visualized under the fluorescent microscope (Olympus, BX53) [ 39 ].…”

“…The robust bioavailability and therapeutic efficacy of DMF is mediated by its potent metabolite MMF through the activation of NRF2 pathway, a key transcription factor involved in antioxidant response [ 38 ]. In our previous study, we have shown that DMF modulates autophagy via NRF2-TIGAR-LAMP2/Cathepsin D pathway in rotenone induced PD model [ 39 ]. Similarly, inducing NRF2 through the administration of DMF can be used to directly induce BNIP3, PINK1/PARKIN expression in the PD disease model and promote mitophagy.…”

Novel potential pharmacological applications of dimethyl fumarate—an overview and update

“…DMF treatments prevent MPTP-induced loss of dopaminergic neurons and striatal dopamine, depletion of tyrosine hydroxylase, GSH and dopamine transporter, and reduce cellular levels of nitrative stress marker 3-nitrotyrosine (3-NT), TNF-α, monocyte chemoattractant protein-1 (MCP-1), α-synuclein oligomers, NF-κB and other oxidative stress or inflammatory markers. More recently, DMF (15–30–60 mg/kg) has been administered to a rotenone-induced mouse model of PD, leading to improvements in the rotenone-induced motor deficits and to decreases in the levels of α-synuclein in brain sections ( Khot et al, 2023 ). Results from this study also remarked a DMF-induced activation of the autophagic pathway, and an inhibition of apoptosis and inflammatory cytokines.…”

Vincamine alleviates brain injury by attenuating neuroinflammation and oxidative damage in a mouse model of Parkinson's disease through the NF‐κB and Nrf2/HO‐1 signaling pathways

“…[24,25] Activating the Nrf2 antioxidant signaling pathway has been demonstrated to exert beneficial effects on hindering the progression of PD. [26,27] Vincamine (chemical structure shown in Figure 1A) is an indole alkaloid obtained from the leaves of Vinca minor, a flowering plant that has been used as a nutritional supplement or antiaging drug for thousands of years. [28] Modern pharmacological studies have revealed that vincamine has antiapoptotic, anti-inflammatory, and antioxidant properties against a variety of central and/or peripheral diseases.…”