Glutathione Peroxidase-1 Knockout Facilitates Memory Impairment Induced by β-Amyloid (1–42) in Mice via Inhibition of PKC βII-Mediated ERK Signaling; Application with Glutathione Peroxidase-1 Gene-Encoded Adenovirus Vector

Shin, Eun Joo; Chung, Yoon Hee; Sharma, Naveen; Nguyen, Bao Trong; Lee, Sung Hoon; Kang, Sang Won; Nah, Seung Yeol; Wie, Myung‐Bok; Nabeshima, Toshitaka; Jeong, Ji Hoon; Kim, Hyoung Chun

doi:10.1007/s11064-020-03147-3

Cited by 24 publications

(13 citation statements)

References 57 publications

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“…Similarly, the cognitive ability of GPX1-knockout mice treated with Aβ1-42 declined significantly, and the activity levels of the βII-isoform of protein kinase C (PKCβII) and extracellular signal−regulated kinase (ERK) in the brain significantly decreased. Re-expression of GPX1 in this mouse brain activated PKCβII-mediated ERK signal transduction to ameliorate Aβ1-42-induced memory impairment (Shin et al, 2020). In addition, studies of GPX4 and GPX1 gene polymorphisms show that certain GPX1 (rs1050450) and GPX4 (rs713041) genotypes are significantly associated with AD patients in a South Brazilian population (da Rocha et al, 2018).…”

Section: Gpx4 and Gpx1mentioning

confidence: 91%

Roles of Selenoproteins in Brain Function and the Potential Mechanism of Selenium in Alzheimer’s Disease

Zhang

Song

2021

Front. Neurosci.

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Selenium (Se) and its compounds have been reported to have great potential in the prevention and treatment of Alzheimer’s disease (AD). However, little is known about the functional mechanism of Se in these processes, limiting its further clinical application. Se exerts its biological functions mainly through selenoproteins, which play vital roles in maintaining optimal brain function. Therefore, selenoproteins, especially brain function-associated selenoproteins, may be involved in the pathogenesis of AD. Here, we analyze the expression and distribution of 25 selenoproteins in the brain and summarize the relationships between selenoproteins and brain function by reviewing recent literature and information contained in relevant databases to identify selenoproteins (GPX4, SELENOP, SELENOK, SELENOT, GPX1, SELENOM, SELENOS, and SELENOW) that are highly expressed specifically in AD-related brain regions and closely associated with brain function. Finally, the potential functions of these selenoproteins in AD are discussed, for example, the function of GPX4 in ferroptosis and the effects of the endoplasmic reticulum (ER)-resident protein SELENOK on Ca2+ homeostasis and receptor-mediated synaptic functions. This review discusses selenoproteins that are closely associated with brain function and the relevant pathways of their involvement in AD pathology to provide new directions for research on the mechanism of Se in AD.

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Section: Gpx4 and Gpx1mentioning

confidence: 91%

Roles of Selenoproteins in Brain Function and the Potential Mechanism of Selenium in Alzheimer’s Disease

Zhang

Song

2021

Front. Neurosci.

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“…We also confirmed whether a U0126 co-treatment affected the activation of the ERK1/2–DRP1 signaling pathway induced by EGCG. As GPx1 activates ERK1/2 phosphorylation [ 62 , 63 , 64 ], the effect of a U0126 co-treatment on EGCG-induced GPx1 upregulation was investigated. Compared with the vehicle, the U0126 co-treatment did not affect the total DRP1 protein level ( Figure 10 A–C and Figure S4 ).…”

Section: Resultsmentioning

confidence: 99%

“…GPx1 removes H 2 O 2 by acting as a cofactor of GSH [ 32 , 33 ], and EGCG increases the GSH level that upregulates GPx1 expression in CA1 neurons [ 34 , 36 ]. Furthermore, GPx1 activates ERK1/2 phosphorylation [ 62 , 63 , 64 ]. Therefore, our findings indicated that the antioxidative activity of EGCG may protect CA1 neurons from impaired mitochondrial elongation induced by ROS.…”

Section: Discussionmentioning

confidence: 99%

EGCG Attenuates CA1 Neuronal Death by Regulating GPx1, NF-κB S536 Phosphorylation and Mitochondrial Dynamics in the Rat Hippocampus following Status Epilepticus

Kim

Kang

2023

Antioxidants

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Epigallocatechin-3-gallate (EGCG) is an antioxidant that directly scavenges reactive oxygen species (ROS) and inhibits pro-oxidant enzymes. Although EGCG protects hippocampal neurons from status epilepticus (SE, a prolonged seizure activity), the underlying mechanisms are not fully understood. As the preservation of mitochondrial dynamics is essential for cell viability, it is noteworthy to elucidate the effects of EGCG on impaired mitochondrial dynamics and the related signaling pathways in SE-induced CA1 neuronal degeneration, which are yet unclear. In the present study, we found that EGCG attenuated SE-induced CA1 neuronal death, accompanied by glutathione peroxidase-1 (GPx1) induction. EGCG also abrogated mitochondrial hyperfusion in these neurons by the preservation of extracellular signal-regulated kinase 1/2 (ERK1/2)–dynamin-related protein 1 (DRP1)-mediated mitochondrial fission, independent of c-Jun N-terminal kinase (JNK) activity. Furthermore, EGCG abolished SE-induced nuclear factor-κB (NF-κB) serine (S) 536 phosphorylation in CA1 neurons. ERK1/2 inhibition by U0126 diminished the effect of EGCG on neuroprotection and mitochondrial hyperfusion in response to SE without affecting GPx1 induction and NF-κB S536 phosphorylation, indicating that the restoration of ERK1/2–DRP1-mediated fission may be required for the neuroprotective effects of EGCG against SE. Therefore, our findings suggest that EGCG may protect CA1 neurons from SE insults through GPx1–ERK1/2–DRP1 and GPx1–NF-κB signaling pathways, respectively.

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“…As for another selenoenzyme, MsrB1 (previously called SELENOR), its level was significantly increased in the SeNa-treated group. Interestingly, numerous studies have indicated an association between GPx1 and Aβ pathology [ 43 , 44 ], modulation of phosphorylated GSK-3β by TrxR activity [ 45 , 46 ], and the effects of SELENOR on synaptic function [ 47 ]. Therefore, our results indicate that different Se compounds induce the activity and expression of different selenoenzymes in the brains of AD mice, which may be the fundamental reason for their different effects on AD pathology.…”

Section: Discussionmentioning

confidence: 99%

Different Effects and Mechanisms of Selenium Compounds in Improving Pathology in Alzheimer’s Disease

et al. 2023

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Owing to the strong antioxidant capacity of selenium (Se) in vivo, a variety of Se compounds have been shown to have great potential for improving the main pathologies and cognitive impairment in Alzheimer’s disease (AD) models. However, the differences in the anti-AD effects and mechanisms of different Se compounds are still unclear. Theoretically, the absorption and metabolism of different forms of Se in the body vary, which directly determines the diversification of downstream regulatory pathways. In this study, low doses of Se-methylselenocysteine (SMC), selenomethionine (SeM), or sodium selenate (SeNa) were administered to triple transgenic AD (3× Tg-AD) mice for short time periods. AD pathology, activities of selenoenzymes, and metabolic profiles in the brain were studied to explore the similarities and differences in the anti-AD effects and mechanisms of the three Se compounds. We found that all of these Se compounds significantly increased Se levels and antioxidant capacity, regulated amino acid metabolism, and ameliorated synaptic deficits, thus improving the cognitive capacity of AD mice. Importantly, SMC preferentially increased the expression and activity of thioredoxin reductase and reduced tau phosphorylation by inhibiting glycogen synthase kinase-3 beta (GSK-3β) activity. Glutathione peroxidase 1 (GPx1), the selenoenzyme most affected by SeM, decreased amyloid beta production and improved mitochondrial function. SeNa improved methionine sulfoxide reductase B1 (MsrB1) expression, reflected in AD pathology as promoting the expression of synaptic proteins and restoring synaptic deficits. Herein, we reveal the differences and mechanisms by which different Se compounds improve multiple pathologies of AD and provide novel insights into the targeted administration of Se-containing drugs in the treatment of AD.

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Glutathione Peroxidase-1 Knockout Facilitates Memory Impairment Induced by β-Amyloid (1–42) in Mice via Inhibition of PKC βII-Mediated ERK Signaling; Application with Glutathione Peroxidase-1 Gene-Encoded Adenovirus Vector

Cited by 24 publications

References 57 publications

Roles of Selenoproteins in Brain Function and the Potential Mechanism of Selenium in Alzheimer’s Disease

Roles of Selenoproteins in Brain Function and the Potential Mechanism of Selenium in Alzheimer’s Disease

EGCG Attenuates CA1 Neuronal Death by Regulating GPx1, NF-κB S536 Phosphorylation and Mitochondrial Dynamics in the Rat Hippocampus following Status Epilepticus

Different Effects and Mechanisms of Selenium Compounds in Improving Pathology in Alzheimer’s Disease

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