Hyperforin attenuates aluminum-induced Aβ production and Tau phosphorylation via regulating Akt/GSK-3β signaling pathway in PC12 cells

Abstract Alzheimer’s disease (AD) is a devastating brain disorder characterized by neurofibrillary tangles and amyloid plaques. Inhibiting Tau protein and amyloid-beta (Aβ) production or removing these molecules are considered potential therapeutic strategies for AD. Genipin is an aglycone and is isolated from the extract of Gardenia jasminoides Ellis fruit. In this study, the effect and molecular mechanisms of genipin on the inhibition of Tau aggregation and Aβ generation were investigated. The results showed that genipin bound to Tau and protected against heparin-induced Tau fibril formation. Moreover, genipin suppressed Tau phosphorylation probably by downregulating the expression of CDK5 and GSK-3β, and activated mTOR-dependent autophagy via the SIRT1/LKB1/AMPK signaling pathway in Tau-overexpressing cells. In addition, genipin decreased Aβ production by inhibiting BACE1 expression through the PERK/eIF2α signaling pathway in N2a/SweAPP cells. These data indicated that genipin could effectively lead to a significant reduction of phosphorylated Tau level and Aβ generation in vitro, suggesting that genipin might be developed into an effective therapeutic complement or a potential nutraceutical for preventing AD.

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Neuroprotective effects of honokiol against beta-amyloid-induced neurotoxicity via GSK-3β and β-catenin signaling pathway in PC12 cells

Neurochemistry International ◽

10.1016/j.neuint.2016.04.014 ◽

2016 ◽

Vol 97 ◽

pp. 8-14 ◽

Cited By ~ 11

Author(s):

Yan-Fang Xian ◽

Siu-Po Ip ◽

Qing-Qiu Mao ◽

Zhi-Xiu Lin

Keyword(s):

Signaling Pathway ◽

Pc12 Cells ◽

Beta Amyloid ◽

Neuroprotective Effects ◽

Gsk 3Β

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Leptin Regulates Tau Phosphorylation through Wnt Signaling Pathway in PC12 Cells

Neurosignals ◽

10.1159/000442616 ◽

2016 ◽

pp. 95-101 ◽

Cited By ~ 2

Author(s):

Zijuan Zhang ◽

Meixia Guo ◽

Juan Zhang ◽

Caixia Du ◽

Ying Xing

Keyword(s):

Wnt Signaling ◽

Signaling Pathway ◽

Pc12 Cells ◽

Wnt Signaling Pathway ◽

Tau Phosphorylation

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I2020T mutant LRRK2 iPSC-derived neurons in the Sagamihara family exhibit increased Tau phosphorylation through the AKT/GSK-3β signaling pathway

Human Molecular Genetics ◽

10.1093/hmg/ddv212 ◽

2015 ◽

Vol 24 (17) ◽

pp. 4879-4900 ◽

Cited By ~ 37

Author(s):

Etsuro Ohta ◽

Tomoko Nihira ◽

Akiko Uchino ◽

Yoichi Imaizumi ◽

Yohei Okada ◽

...

Keyword(s):

Signaling Pathway ◽

Tau Phosphorylation ◽

Mutant Lrrk2 ◽

Gsk 3Β

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Vina-Ginsenoside R4 from Panax ginseng Leaves Alleviates 6-OHDA-Induced Neurotoxicity in PC12 Cells Via the PI3K/Akt/GSK-3β Signaling Pathway

Journal of Agricultural and Food Chemistry ◽

10.1021/acs.jafc.0c06474 ◽

2020 ◽

Vol 68 (51) ◽

pp. 15239-15248

Author(s):

Yanyan Luo ◽

Yunyao Jiang ◽

Yang He ◽

Ting Shen ◽

Lilian Ji ◽

...

Keyword(s):

Signaling Pathway ◽

Pc12 Cells ◽

Panax Ginseng ◽

Gsk 3Β

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Icariin protects against sodium azide—induced neurotoxicity by activating the PI3K/Akt/GSK-3β signaling pathway

PeerJ ◽

10.7717/peerj.8955 ◽

2020 ◽

Vol 8 ◽

pp. e8955

Author(s):

Ying Zhang ◽

Nanqu Huang ◽

Hao Lu ◽

Juan Huang ◽

Hai Jin ◽

...

Keyword(s):

Signaling Pathway ◽

Pc12 Cells ◽

Sodium Azide ◽

Pc12 Cell ◽

Glucose Concentration ◽

Cell Damage ◽

Chinese Herb ◽

Glucose Consumption ◽

Neuroprotective Effects ◽

Gsk 3Β

Background Icariin (ICA) is one of the major active flavonoids extracted from the traditional Chinese herb Epimedium brevicornum Maxim and has been shown to have neuroprotective effects. This study was designed to investigate the effect of ICA on sodium azide (NaN3)-induced rat adrenal pheochromocytoma (PC12) cell damage and to further examine the underlying mechanisms. Methods To explore its possible mechanism, we used NaN3 (50 mM)-induced neuronal PC12 cell damage. Cell viability was evaluated by CCK-8 and lactate dehydrogenase (LDH) assays. Mitochondrial membrane potential (MMP) was detected by JC-1. Glucose concentration was assessed by the glucose oxidase method. The role of ICA in the PI3K/Akt/GSK-3β signaling pathway was explored by Western blotting. Results The results indicate that pretreatment with ICA reduced NaN3-induced cell damage and significantly reduced the leakage rate of LDH in PC12 cells. ICA pretreatment increased the MMP and a decrease in glucose concentration indicate increased glucose consumption. Furthermore, the protein levels of p-PI3K (p85), PI3K-110α, p-Ser473-Akt and p-Ser9-GSK-3β were markedly decreased in PC12 cells after NaN3 treatment for 24 h, whereas these effects were reverted after pretreatment with ICA. Tau phosphorylation at the Ser396/404 and Thr217 sites was significantly decreased by pretreatment with ICA. Conclusions These results suggest that ICA protects against NaN3-induced neurotoxicity in PC12 cells by activating the PI3K/Akt/GSK-3β signaling pathway.

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Salidroside Protection Against Oxidative Stress Injury Through the Wnt/β-Catenin Signaling Pathway in Rats with Parkinson’s Disease

Cellular Physiology and Biochemistry ◽

10.1159/000489365 ◽

2018 ◽

Vol 46 (5) ◽

pp. 1793-1806 ◽

Cited By ~ 20

Author(s):

Dong-Mei Wu ◽

Xin-Rui Han ◽

Xin Wen ◽

Shan Wang ◽

Shao-Hua Fan ◽

...

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Protective Effect ◽

Signaling Pathway ◽

Pc12 Cells ◽

Protein Levels ◽

Licl Treatment ◽

Gsk 3Β

Background/Aims: Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease, and recent studies suggested that oxidative stress (OS) contributes to the cascade that leads to dopamine cell degeneration in PD. In this study, we hypothesized that salidroside (SDS) offers protection against OS injury in 6-hydroxydopamine (6-OHDA) unilaterally lesioned rats as well as the underlying mechanism. Methods: SDS and LiCl (activators of the Wnt/β-catenin signaling pathway) administration alone and in combination with 6-OHDA injection in rats was performed 3 days before modeling for 17 consecutive days to verify the regulatory mechanism by which SDS affects the Wnt/β-catenin signaling pathway as well as to evaluate the protective effect of SDS on PD in relation to OS in vivo. In addition, pheochromocytoma 12 (PC12) cells were incubated with 10 µmol/L SDS or LiCl alone or with both in combination for 1 h followed by a 24-h incubation with 100 µmol/L 6-OHDA to obtain in vitro data. Results: In vivo the administration of LiCl was found to ameliorate behavioral deficits and dopaminergic neuron loss; increase superoxide dismutase (SOA) activity, glutathione peroxidase (GSH-Px) levels, and glycogen synthase kinase 3β phosphorylation (GSK-3β-Ser9); reduce malondialdehyde (MDA) accumulation in the striatum and the GSK-3β mRNA level; as well as elevate β-catenin and cyclinD1 mRNA and protein levels in 6-OHDA-injected rats. This SDS treatment regimen was found to strengthen the beneficial effect of LiCl on 6-OHDA-injected rats. In vitro LiCl treatment decreased the toxicity of 6-OHDA on PC12 cells and prevented apoptosis. Additionally, LiCl treatment increased SOA activity, GSH-Px levels, and GSK-3β-Ser9 phosphorylation; decreased MDA accumulation in the striatum and GSK-3β mRNA levels; as well as increased β-catenin and cyclinD1 mRNA and protein levels in 6-OHDA-treated PC12 cells. Additionally, SDS treatment increased the protective effect of LiCl on 6-OHDA-treated PC12 cells. Conclusion: Evidence from experimental models suggested that SDS may confer neuroprotection against the neurotoxicity of 6-OHDA in response to OS injury and showed that these beneficial effects may be related to regulation of the Wnt/β-catenin signaling pathway. Therefore, SDS might be a potential therapeutic agent for treating PD.

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