Quercetin reduces APP expression, oxidative stress and mitochondrial dysfunction in the N2a/APPswe cells via ERK1/2 and AKT pathways

Tang, Zhi; Guo, Min; Peng, Yaqian; Xiao, Yan; Zhang, Ting; Ni, Ruiqing; Qi, Xiaolan

doi:10.1101/2022.09.18.508406

Cited by 6 publications

(4 citation statements)

References 48 publications

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“…Next, western blotting was performed to investigate the changes after treatment in the level of presynaptic proteins (SNAP25 and synaptophysin) and postsynaptic proteins (PSD95); phosphorylated-tau (p-tau) and total-tau (t-tau); phosphorylated-ERK (p-ERK) and total-ERK (t-ERK); phosphorylated-GSK3β (p-GSK3β) and total-GSK3β (t-GSK3β) proteins; mitochondrial fission protein (dynamin-related protein 1, Drp1) and fusion proteins (mitofusin-1, Mfn1; mitofusin-2, Mfn2) as previously described [38, 39]. The antibodies used are listed in Supplementary Table 1 .…”

Section: Methodsmentioning

confidence: 99%

Myricetin protected against Aβ oligomer-induced synaptic impairment, mitochondrial function and oxidative stress in SH-SY5Y cells via ERK1/2/GSK-3β pathways

Wang

Tang

Deng

et al. 2023

Preprint

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Alzheimers disease is characterized by abnormal β-amyloid (Aβ) plaque accumulation, tau hyperphosphorylation, reactive oxidative stress, mitochondrial dysfunction and synaptic loss. Myricetin, a dietary flavonoid, has been shown to have neuroprotective effects in vitro and in vivo. Here, we aimed to elucidate the mechanism and pathways involved in myricetin protective effect on the toxicity induced by the Aβ42 oligomer. Neuronal SH-SY5Y cells were pretreated with myricetin before incubation with Aβ42 oligomer. The levels of pre- and post-synaptic proteins, mitochondrial division and fusion proteins, glycogen synthase kinase-3β (GSK-β) and extracellular regulated kinase (ERK) 1/2 were assessed by Western blotting. Flow cytometry assays for mitochondrial membrane potential (JC1) and reactive oxidative stress, as well immunofluorescence staining for lipid peroxidation (4-HNE) and DNA oxidation (8-OHdG), were performed. We found that myricetin prevented Aβ42 oligomer-induced tau phosphorylation and the reduction in pre/postsynaptic proteins. In addition, myricetin reduced reactive oxygen species generation, lipid peroxidation, and DNA oxidation induced by the Aβ42 oligomer. Moreover, myricetin prevented the Aβ42 oligomer-induced reduction in mitochondrial fusion proteins (mitofusin-1, mitofusin-2), fission protein (dynamin-related protein 1) phosphorylation, and mitochondrial membrane potential via the associated GSK-3β and ERK 1/2 signaling pathways. In conclusion, this study provides new insight into the neuroprotective mechanism of myricetin against Aβ42 oligomer-induced toxicity.

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Section: Methodsmentioning

confidence: 99%

Myricetin protected against Aβ oligomer-induced synaptic impairment, mitochondrial function and oxidative stress in SH-SY5Y cells via ERK1/2/GSK-3β pathways

Wang

Tang

Deng

et al. 2023

Preprint

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“…Cell viability was examined using Cell Counting Kit-8 (CCK-8) as previously described [55]. Briefly, N2a/APP cells were seeded in 96-well plates at nearly 5000 cells per well.…”

Section: Methodsmentioning

confidence: 99%

Gastrodin ameliorates synaptic impairment, reestablishes mitochondrial membrane potential and reduces oxidative stress in N2a/APP cells through ERK1/2 and GSK-3β pathways

Tang

Peng

Wang

et al. 2023

Preprint

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Alzheimer's disease (AD) is featured by abnormal &beta-amyloid (Abeta) deposition, neurofibrillary tangle formation, downstream mitochondrial dysfunction, oxidative stress, and synaptic loss. Gastrodin, a phenolic glycoside, has shown neuroprotective effect and used in the treatment of a range of brain diseases. Here we aim to assess the mechanisms and signaling pathways involved in the neuroprotective effect of gastrodin in murine neuroblastoma N2a cells expressing human Swedish mutant amyloid precursor protein (N2a/APP). The levels of pre- and postsynaptic proteins, amyloid precursor protein C-terminal fragments (APP-CTFs), levels of tau, glycogen synthase kinase-3beta (GSK-3beta), extracellular regulated kinase (ERK), and c-Jun N-terminal Kinase (JNK) were assessed by Western blotting. Flow cytometry assays for mitochondrial membrane potential (JC1) and reactive oxidative stress, as well as immunofluorescence staining for lipid peroxidation (4-hydroxynonenal) and DNA oxidation (8-hydroxy-2'-deoxyguanosine), were performed. We found that gastrodin treatment increased the levels of presynaptic SNAP25, synaptophysin, and postsynaptic PSD95, reduced phosphorylated tau protein Ser396, and APP-CTFs in N2a/APP cells. In addition, gastrodin reduced the levels of reactive oxygen species generation, lipid peroxidation, and DNA oxidation, reestablished mitochondrial membrane potential. Upregulated levels of phosphorylated-GSK-3beta, reduced levels of phosphorylated-ERK, and phosphorylated-JNK were involved the protective effect of gastrodin. In conclusion, we demonstrated a neuroprotective effect of gastrodin in N2a/APP cell line.

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“…mAS cells were homogenized in ice-cold RIPA lysis buffer containing freshly added protease inhibitor (Sigma) [41]. Samples (40 μg protein/lane) were separated by 10% Bis-Tris gels and semidry transferred to polyvinylidene fluoride (PVDF) membranes (0.45 μm pore size, Millipore).…”

Section: Immunoblotting Analysismentioning

confidence: 99%

NRF2 Deficiency Promotes Ferroptosis of Astrocytes Mediated by Oxidative Stress in Alzheimer’s Disease

Tang,

Chen,

Guo

et al. 2024

Mol Neurobiol

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Oxidative stress is involved in the pathogenesis of Alzheimer's disease (AD), which is linked to reactive oxygen species (ROS), lipid peroxidation, and neurotoxicity. Emerging evidence suggests a role of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a major source of antioxidant response elements in AD. The molecular mechanism of oxidative stress and ferroptosis in astrocytes in AD is not yet fully understood. Here, we aim to investigate the mechanism by which Nrf2 regulates the ferroptosis of astrocytes in AD. Postmortem frontal cortex tissues from patients with AD and nondemented controls and brain tissue from the 3×Tg AD mouse model and wild-type mice (10 months old) were used. Immunofluorescence staining for Nrf2, the ROS marker NADPH oxidase 4 (NOX4), and GFAP was performed.We further induced Nrf2 deficiency in mouse astrocytes by using RNAi and assessed the changes in ROS, ferroptosis, lipid peroxidation, and mitochondrial dysfunction by using western blotting and immunofluorescence staining. We found decreased expression of Nrf2 and upregulated expression of NOX4 in the frontal cortex from patients with AD and in the cortex of 3×Tg mice compared to control mice. We demonstrated that Nrf2 deficiency led to ferroptosis-dependent oxidative stress-induced ROS with downregulated heme oxygenase-1 and glutathione peroxidase 4 and upregulated cystine glutamate expression. Moreover, Nrf2 deficiency increased lipid peroxidation, DNA oxidation, and mitochondrial fragmentation in mouse astrocytes. In conclusion, these results suggest that Nrf2 promotes ferroptosis of astrocytes involving oxidative stress in AD..

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Quercetin reduces APP expression, oxidative stress and mitochondrial dysfunction in the N2a/APPswe cells via ERK1/2 and AKT pathways

Cited by 6 publications

References 48 publications

Myricetin protected against Aβ oligomer-induced synaptic impairment, mitochondrial function and oxidative stress in SH-SY5Y cells via ERK1/2/GSK-3β pathways

Myricetin protected against Aβ oligomer-induced synaptic impairment, mitochondrial function and oxidative stress in SH-SY5Y cells via ERK1/2/GSK-3β pathways

Gastrodin ameliorates synaptic impairment, reestablishes mitochondrial membrane potential and reduces oxidative stress in N2a/APP cells through ERK1/2 and GSK-3β pathways

NRF2 Deficiency Promotes Ferroptosis of Astrocytes Mediated by Oxidative Stress in Alzheimer’s Disease

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