scholarly journals Glutamine Improves Oxidative Stress through the Wnt3a/β-Catenin Signaling Pathway in Alzheimer’s Disease In Vitro and In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Yuan Wang ◽  
Qiang Wang ◽  
Jie Li ◽  
Gang Lu ◽  
Zhibin Liu
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Pc12 Cells ◽  
Stress Injury ◽  
Mda Content ◽  
Samp8 Mice

Background/Aims. Alzheimer’s disease (AD) is the most common neurodegenerative disease, and all researchers working in this field agree that oxidative stress is intimately associated with Alzheimer disease. In this study, we hypothesized that glutamine (Gln) offers protection against oxidative stress injury in SAMP8 mice as well as the underlying mechanism. Methods. The SAMP8 mice received glutamine intragastrically for 8 consecutive weeks to evaluate the protective effect of glutamine on oxidative stress in AD mice involving Wnt3a/β-catenin signaling pathway. In addition, rat pheochromocytoma tumor cell line PC12 was pretreated with 32 μM glutamine for 2 h followed by 24 h incubation with 40 μM Aβ25-35 to obtain in vitro data. Results. In vivo the administration of glutamine was found to ameliorate behavioral deficits and neuron damage, increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-XP) activity, reduce the malondialdehyde (MDA) content, and activate the Wnt3a/β-catenin signaling pathway in SAMP8 mice. In vitro glutamine treatment decreased the toxicity of Aβ25-35 on PC12 cells and prevented apoptosis. Additionally, glutamine treatment increased SOD and GSH-XP activity and decreased MDA content and increased Wnt3a and β-catenin protein levels. Interestingly, the DKK-1 (Wnt3a/β-catenin pathway inhibitor) decreased the antioxidant capacity of glutamine in Aβ25-35-treated PC12 cells. Conclusion. This study suggests that glutamine could protect against oxidative stress-induced injury in AD mice via the Wnt3a/β-catenin signaling pathway.

Targeting PPARalpha in Alzheimer's Disease

2018 ◽  
Vol 15 (4) ◽  
pp. 345-354 ◽  
Author(s):  
Barbara D'Orio ◽  
Anna Fracassi ◽  
Maria Paola Cerù ◽  
Sandra Moreno
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Redox Homeostasis ◽  
Antioxidant Response ◽  
Peroxisome Proliferator ◽  
Prevailing Paradigm

Background: The molecular mechanisms underlying Alzheimer's disease (AD) are yet to be fully elucidated. The so-called “amyloid cascade hypothesis” has long been the prevailing paradigm for causation of disease, and is today being revisited in relation to other pathogenic pathways, such as oxidative stress, neuroinflammation and energy dysmetabolism. The peroxisome proliferator-activated receptors (PPARs) are expressed in the central nervous system (CNS) and regulate many physiological processes, such as energy metabolism, neurotransmission, redox homeostasis, autophagy and cell cycle. Among the three isotypes (α, β/δ, γ), PPARγ role is the most extensively studied, while information on α and β/δ are still scanty. However, recent in vitro and in vivo evidence point to PPARα as a promising therapeutic target in AD. Conclusion: This review provides an update on this topic, focussing on the effects of natural or synthetic agonists in modulating pathogenetic mechanisms at AD onset and during its progression. Ligandactivated PPARα inihibits amyloidogenic pathway, Tau hyperphosphorylation and neuroinflammation. Concomitantly, the receptor elicits an enzymatic antioxidant response to oxidative stress, ameliorates glucose and lipid dysmetabolism, and stimulates autophagy.

scholarly journals Mechanistic Aspects of Apiaceae Family Spices in Ameliorating Alzheimer’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1571
Author(s):  
Niti Sharma ◽  
Mario A. Tan ◽  
Seong Soo A. An
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Scientific Literature ◽  
Comprehensive Evaluation ◽  
Amyloid Plaque ◽  
Plaque Formation ◽  
New Strategies

Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases worldwide. In an effort to search for new strategies for treating AD, natural products have become candidates of choice. Plants are a rich source of bioactive and effective compounds used in treating numerous diseases. Various plant extracts are known to display neuroprotective activities by targeting different pathophysiological pathways in association with the diseases, such as inhibiting enzymes responsible for degrading neurotransmitters, reducing oxidative stress, neuroprotection, inhibiting amyloid plaque formation, and replenishing mitochondrial function. This review presented a comprehensive evaluation of the available scientific literature (in vivo, in vitro, and in silico) on the neuroprotective mechanisms displayed by the extracts/bioactive compounds from spices belonging to the Apiaceae family in ameliorating AD.

scholarly journals Overexpression of miR-506-3p Aggravates DBP-Induced Testicular Oxidative Stress in Rats by Downregulating ANXA5 via Nrf2/HO-1 Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Min Tang ◽  
Lei Zhang ◽  
Zheng Zhu ◽  
Ran Li ◽  
Shangqian Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Male Rats ◽  
Adolescent Male ◽  
Seminiferous Tubules ◽  
Stress Injury ◽  
Oxidative Stress Injury ◽  
Testicular Injury

Background. Di-N-butylphthalate (DBP) is a kind of unique endocrine toxicity linked to hormonal disruptions that affects the male reproductive system and has given rise to more and more attention. However, the mechanism of DBP-induced testicular injury remains unclear. Here, the objective of this study was to investigate the potential molecular mechanism of miR-506-3p in DBP-induced rat testicular oxidative stress injury via ANXA5 (Annexin A5)/Nrf2/HO-1 signaling pathway. Methods. In vivo, a total of 40 adolescent male rats were treated from 2 weeks with 800 mg/kg/day of DBP in 1 mL/kg corn oil administered daily by oral gavage. Among them, some rats were also injected subcutaneously with 2 nmol agomir-506-3p and/or 10 nmol recombinant rat ANXA5. The pathomorphological changes of testicular tissue were assessed by histological examination, and the antioxidant factors were evaluated. Subsequently, ANXA5, Nrf2, and its dependent antioxidant enzymes, such as HO-1, NQO1, and GST, were detected by Western blotting or immunohistochemical staining. In vitro, TM3 cells (Leydig cells) were used to detect the cell activity by CCK-8 and the transfection in the DBP-treated group. Results. Differentially expressed miRNAs between the DBP-treated and normal rats were analyzed, and qRT-PCR showed miR-506-3p was highly expressed in testicular tissues of the DBP-treated rats. DBP-treated rats presented severe inflammatory infiltration, increased abnormal germ cells, and missed cell layers frequently existed in seminiferous tubules, resulted in oxidative stress and decreased testicular function. Meanwhile, upregulation of miR-506-3p aggravated the above changes. In addition, miR-506-3p directly bound to ANXA5, and overexpression of miR-506-3p could reduce the ANXA5 expression and also decrease the protein levels of Nrf2/HO-1 signaling pathway. Additionally, we found that recombinant rat ANXA5 reversed the DBP-treated testicular oxidative stress promoting injury of miR-506-3p in rats. In vivo results were reproduced in in vitro experiments. Conclusions. This study provided evidence that miR-506-3p could aggravate the DBP-treated testicular oxidative stress injury in vivo and in vitro by inhibiting ANXA5 expression and downregulating Nrf2/HO-1 signaling pathway, which might provide novel understanding in DBP-induced testicular injury therapy.

Inhibiting α1-adrenergic Receptor Signaling Pathway Ameliorates Alzheimer’s Disease Type Pathologies and Behavioral Deficits in an AD Mouse Model

2021 ◽  
Author(s):  
Zhong-Yuan Yu ◽  
Xu Yi ◽  
Ye-Ran Wang ◽  
Gui-Hua Zeng ◽  
Cheng-Rong Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Neuronal Loss ◽  
Behavioral Deficits ◽  
Bace1 Expression ◽  
Receptor Signaling Pathway ◽  
Gsk 3Β

Abstract Background The role of α1 adrenergic receptors (α1-ARs) signaling pathway in the pathogenesis of Alzheimer’s disease (AD) has rarely been investigated. Clarifying pathophysiological functions of α1-ARs in the AD brain is helpful for better understanding the pathogenesis and screening novel therapeutic target of AD. Methods This study included 2 arms of in vivo investigations: 1) 6-month-old female APPswe/PS1 mice were intravenously treated with AAV-PHP.eB-shRNA (ARs)-GFP or AAV-PHP.eB-GFP for 3 months. 2) 3-month-old female APPswe/PS1 mice were daily treated with 0.5 mg/kg terazosin or equal saline for 6 months. SH-SY5Y cell lines bearing human Amyloid precurssor protein were treated with terazosin or saline for investigating possible mechanisms. Results α1-ARs knockdown mice exhibited improved behavioral performances than control mice. α1-ARs knockdown mice had significantly lower brain amyloid burden, as reflected by soluble Aβ species, compact and total plaques, than control mice. The α1-ARs inhibitor terazosin substantially reduced Aβ deposition, attenuated downstream pathologies including Tau hyperphosphorylation, glial activation, neuronal loss, synaptic dysfunction, and rescued behavioral deficits of APPswe/PS1 mice. In vitro investigation demonstrated that α1-ARs inhibition down-regulated BACE1 expression, and promoted ser9 phosphorylation of GSK-3β, thus reduced Aβ production. Conclusions This study indicates that inhibition of α1-ARs signaling pathway might represent a promising therapeutic strategy for AD.

scholarly journals Procyanidins Extracted from Lotus Seedpod Ameliorate Amyloid-β-Induced Toxicity in Rat Pheochromocytoma Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Hao Huang ◽  
Peipei Yan ◽  
Taoping Sun ◽  
Xiaoxing Mo ◽  
Jiawei Yin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pc12 Cells ◽  
Senile Plaque ◽  
Critical Role ◽  
Amyloid Β ◽  
Bdnf Signaling ◽  
Lotus Seedpod

Alzheimer’s disease (AD) is a progressive neurodegenerative disease, which is characterized by extracellular senile plaque deposits, intracellular neurofibrillary tangles, and neuronal apoptosis. Amyloid-β (Aβ) plays a critical role in AD that may cause oxidative stress and downregulation of CREB/BDNF signaling. Anti-Aβ effect has been discussed as a potential therapeutic strategy for AD. This study aimed to identify the amelioration of procyanidins extracted from lotus seedpod (LSPC) on Aβ-induced damage with associated pathways for AD treatment. Rat pheochromocytoma (PC12) cells incubated with Aβ25–35 serve as an Aβ damage model to evaluate the effect of LSPC in vitro. Our findings illustrated that LSPC maintained the cellular morphology from deformation and reduced apoptosis rates of cells induced by Aβ25–35. The mechanisms of LSPC to protect cells from Aβ-induced damage were based on its regulation of oxidation index and activation of CREB/BDNF signaling, including brain-derived neurotrophic factor (BDNF) and phosphorylation of cAMP-responsive element-binding (CREB), protein kinase B (also known as AKT), and the extracellular signal-regulated kinase (ERK). Of note, by high-performance liquid chromatography-tandem mass spectroscopy (LC-MS/MS), several metabolites were detected to accumulate in vivo, part of which could take primary responsibility for the amelioration of Aβ-induced damage on PC12 cells. Taken together, our research elucidated the effect of LSPC on neuroprotection through anti-Aβ, indicating it as a potential pretreatment for Alzheimer’s disease.

scholarly journals XinJiaCongRongTuSiZiWan Protects TP-Induced Rats from Oxidative Stress Injury via Mitophagy Mediated PINK1/ Parkin Signaling Pathway

2021 ◽  
Author(s):  
Jin Yan ◽  
Disi Deng ◽  
Min Liu ◽  
Yeke Wu ◽  
Keming Wu
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Atp Content ◽  
Stress Injury ◽  
Primordial Follicles ◽  
Apoptosis Rate ◽  
Oxidative Stress Injury

Abstract Background: Oxidative stress is one of main molecular mechanisms involved in toxicity of triptolide (TP). Although our group has discovered the effectiveness of XinJiaCongRongTuSiZiWan (XJCRTSZW) on premature ovarian failure (POF) and polycystic ovary syndrome (PCOS), whether the protective role of XJCRTSZW being associated with oxidative stress is still totally understood. Methods: Adult female Sprague-Dawley rats and human ovarian granulosa cell lines were treated with TP, and then treated with XinJiaCongRongTuSiZiWan (XJCRTSZW). Histological analysis and follicle count were executed using H&E staining. Hormone (E2, AMH, P, FSH and LH) concentrations, oxidative stress indicators (SOD and MDA), apoptosis rate, ATP content, mitochondrial membrane potential (MMP), cell viability, mitophagy and relative mRNA and protein levels (LC3-Ⅱ/LC3-Ⅰ, p62, Hsp60, PINK1 and Parkin) were detected by ELISA, commercial biochemical detection kits, flow cytometry, JC-1 staining, CCK-8, transmission electron microscope and western blotting respectively. Results: XJCRTSZW treatment observably ameliorated the TP-induced the pathological symptoms, including the decreased primordial follicles, primary follicles and secondary follicles numbers in the cortical area, the increased numbers of atretic follicles, necrotic and shedding, and nuclear constriction and collapse with cystic dilatation in vivo. Furthermore, XJCRTSZW treatment observably enhanced the TP-induced reduction of E2, AMH and P concentrations, SOD concentrations, ATP content, MMP, p62 and Hsp60 mRNA and protein level, but, diminished the TP-induced elevation of FSH and LH concentrations, MDA level, ROS level, apoptosis rate, mitophagy, and the mRNA and protein expression of LC3-Ⅱ/LC3-Ⅰ, PINK1 and Parkin both in vivo and in vitro. In addition, XJCRTSZW treatment markedly increased the TP-induced reduction of cell viability in vitro.Conclusion: XinJiaCongRongTuSiZiWan protects TP-induced rats from oxidative stress injury via mitophagy mediated PINK1/ Parkin signaling pathway.

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