Electroacupuncture Promotes Autophagy by Regulating the AKT/mTOR Signaling Pathway in Temporal Lobe Epilepsy

Gao, Dongsheng; Ma, Linqing; Xie, Yan; Xiao, Bo; Xue, Shouru; Xiao, Wenbiao; Zhou, You; Cai, Xiuying; Yang, Xiaoyan

doi:10.1007/s11064-022-03634-9

Cited by 8 publications

(3 citation statements)

References 33 publications

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“…Furthermore, they observed a reduction in neurogenesis during epileptogenesis when this pathway was blocked. Previous research found electroacupuncture treatment promotes autophagy during epilepsy onset by significantly downregulating the AKT/mTOR signaling pathway, which is consistent with our research (24). Then, we conducted the GSEA, and the result showed that the top 4 pathways were T-cell receptor signaling pathway, cytokine receptor interaction, ribosome, and natural killer cell-mediated cytotoxicity.…”

Section: Discussionsupporting

confidence: 87%

Identification and verification of ferroptosis-related genes in the pathology of epilepsy: insights from CIBERSORT algorithm analysis

Xu,

Chu,

Chen

et al. 2023

Front. Neurol.

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BackgroundEpilepsy is a neurological disorder characterized by recurrent seizures. A mechanism of cell death regulation, known as ferroptosis, which involves iron-dependent lipid peroxidation, has been implicated in various diseases, including epilepsy.ObjectiveThis study aimed to provide a comprehensive understanding of the relationship between ferroptosis and epilepsy through bioinformatics analysis. By identifying key genes, pathways, and potential therapeutic targets, we aimed to shed light on the underlying mechanisms involved in the pathogenesis of epilepsy.Materials and methodsWe conducted a comprehensive analysis by screening gene expression data from the Gene Expression Omnibus (GEO) database and identified the differentially expressed genes (DEGs) related to ferroptosis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to gain insights into the biological processes and pathways involved. Moreover, we constructed a protein–protein interaction (PPI) network to identify hub genes, which was further validated using the receiver operating characteristic (ROC) curve analysis. To explore the relationship between immune infiltration and genes, we employed the CIBERSORT algorithm. Furthermore, we visualized four distinct interaction networks—mRNA–miRNA, mRNA–transcription factor, mRNA–drug, and mRNA–compound—to investigate potential regulatory mechanisms.ResultsIn this study, we identified a total of 33 differentially expressed genes (FDEGs) associated with epilepsy and presented them using a Venn diagram. Enrichment analysis revealed significant enrichment in the pathways related to reactive oxygen species, secondary lysosomes, and ubiquitin protein ligase binding. Furthermore, GSVA enrichment analysis highlighted significant differences between epilepsy and control groups in terms of the generation of precursor metabolites and energy, chaperone complex, and antioxidant activity in Gene Ontology (GO) analysis. Furthermore, during the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, we observed differential expression in pathways associated with amyotrophic lateral sclerosis (ALS) and acute myeloid leukemia (AML) between the two groups. To identify hub genes, we constructed a protein–protein interaction (PPI) network using 30 FDEGs and utilized algorithms. This analysis led to the identification of three hub genes, namely, HIF1A, TLR4, and CASP8. The application of the CIBERSORT algorithm allowed us to explore the immune infiltration patterns between epilepsy and control groups. We found that CD4-naïve T cells, gamma delta T cells, M1 macrophages, and neutrophils exhibited higher expression in the control group than in the epilepsy group.ConclusionThis study identified three FDEGs and analyzed the immune cells in epilepsy. These findings pave the way for future research and the development of innovative therapeutic strategies for epilepsy.

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Section: Discussionsupporting

confidence: 87%

Identification and verification of ferroptosis-related genes in the pathology of epilepsy: insights from CIBERSORT algorithm analysis

Xu,

Chu,

Chen

et al. 2023

Front. Neurol.

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“…mTOR is a serine/threonine protein kinase in the PI3K-related kinase (PIKK) family. AKT blocks the negative regulation of small G protein Rheb by TSC1/2 and indirectly activates mTOR complex 1 (mTORC1) which is involved in the critical regulation of cellular autophagy [ 183 ]. OS injury initiates autophagy by inhibiting the PI3K/AKT signaling pathway, promoting the dissociation between mTORC1 and ULK1, further phosphorylating autophagy-related proteins such as Atg13 [ 184 ].…”

Section: Os-related Signaling Pathways In Ovarian Agingmentioning

confidence: 99%

The role of oxidative stress in ovarian aging: a review

et al. 2022

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Ovarian aging refers to the process by which ovarian function declines until eventual failure. The pathogenesis of ovarian aging is complex and diverse; oxidative stress (OS) is considered to be a key factor. This review focuses on the fact that OS status accelerates the ovarian aging process by promoting apoptosis, inflammation, mitochondrial damage, telomere shortening and biomacromolecular damage. Current evidence suggests that aging, smoking, high-sugar diets, pressure, superovulation, chemotherapeutic agents and industrial pollutants can be factors that accelerate ovarian aging by exacerbating OS status. In addition, we review the role of nuclear factor E2-related factor 2 (Nrf2), Sirtuin (Sirt), mitogen-activated protein kinase (MAPK), protein kinase B (AKT), Forkhead box O (FoxO) and Klotho signaling pathways during the process of ovarian aging. We also explore the role of antioxidant therapies such as melatonin, vitamins, stem cell therapies, antioxidant monomers and Traditional Chinese Medicine (TCM), and investigate the roles of these supplements with respect to the reduction of OS and the improvement of ovarian function. This review provides a rationale for antioxidant therapy to improve ovarian aging.

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“…Rapamycin induces early activation of the autophagy cascade via blockade of mTOR, while activation of mTOR inhibits the formation of autophagosomes (Crino, 2016). By analyzing the differentially expressed genes (DEGs) in epilepsy rat models with or without electroacupuncture treatment, the functional enrichment of DEGs was found mainly in the mTOR signaling pathway and autophagy (Gao et al., 2022). Thus, there is a reliable correlation between mTOR‐dependent autophagy and seizure onset and seizure‐induced neuronal damage.…”

Section: The Role Of the Mtor Signaling Pathway In Epilepsymentioning

confidence: 99%

Advances in the mTOR signaling pathway and its inhibitor rapamycin in epilepsy

et al. 2023

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Introduction: Epilepsy is one of the most common and serious brain syndromes and has adverse consequences on a patient's neurobiological, cognitive, psychological, and social wellbeing, thereby threatening their quality of life. Some patients with epilepsy experience poor treatment effects due to the unclear pathophysiological mechanisms of the syndrome. Dysregulation of the mammalian target of the rapamycin (mTOR) pathway is thought to play an important role in the onset and progression of some epilepsies.Methods: This review summarizes the role of the mTOR signaling pathway in the pathogenesis of epilepsy and the prospects for the use of mTOR inhibitors. Results:The mTOR pathway functions as a vital mediator in epilepsy development through diverse mechanisms, indicating that the it has great potential as an effective target for epilepsy therapy. The excessive activation of mTOR signaling pathway leads to structural changes in neurons, inhibits autophagy, exacerbates neuron damage, affects mossy fiber sprouting, enhances neuronal excitability, increases neuroinflammation, and is closely associated with tau upregulation in epilepsy. A growing number of studies have demonstrated that mTOR inhibitors exhibit significant antiepileptic effects in both clinical applications and animal models. Specifically, rapamycin, a specific inhibitor of TOR, reduces the intensity and frequency of seizures. Clinical studies in patients with tuberous sclerosis complex have shown that rapamycin has the function of reducing seizures and improving this disease. Everolimus, a chemically modified derivative of rapamycin, has been approved as an added treatment to other antiepileptic medicines. Further explorations are needed to evaluate the therapeutic efficacy andThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Electroacupuncture Promotes Autophagy by Regulating the AKT/mTOR Signaling Pathway in Temporal Lobe Epilepsy

Cited by 8 publications

References 33 publications

Identification and verification of ferroptosis-related genes in the pathology of epilepsy: insights from CIBERSORT algorithm analysis

Identification and verification of ferroptosis-related genes in the pathology of epilepsy: insights from CIBERSORT algorithm analysis

The role of oxidative stress in ovarian aging: a review

Advances in the mTOR signaling pathway and its inhibitor rapamycin in epilepsy

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