Expression of Akt1 and p-Akt1 in peripheral T cell subsets of multiple sclerosis patients

Öktelik, Fatma Betül; Yılmaz, Vuslat; Türkoğlu, Recai; Akbayır, Ece; Tüzün, Erdem; Deniz, Günnur; Çınar, Sezgi

doi:10.1007/s13760-020-01518-9

Cited by 5 publications

(3 citation statements)

References 17 publications

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“…For instance, the expression of AKT-1 and phosphorylated-Akt1 (p-Akt1) decreased in CD4+ T cell and regulatory T (Treg) cells of RRMS. [ 37 ] Numerous studies have found IL-4 and IL-4R to be associated with MS. [ 38 ] Increased TNF levels were previously the meninges and CSF in MS. [ 39 ] Moreover, miR-155-5p is known to regulate the pathological process of MS by targeting the aforementioned genes. Sanders et al [ 40 ] reported miR-155-5p downregulation in SPMS CD4+ T cells, which targeted SOCS6.…”

Section: Resultsmentioning

confidence: 99%

Construction of miRNA-regulated drug-pathway network to screen drug repurposing candidates for multiple sclerosis

Kong

Wang²,

Cao³

et al. 2022

Medicine

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Given the high disability rate of multiple sclerosis (MS), there is a need for safer and more effective therapeutic agents. Existing literature highlights the prominent roles of miRNA in MS pathophysiology. Nevertheless, there are few studies that have explored the usefulness of existing drugs in treating MS through potential miRNA-modulating abilities.The current investigation identifies genes that may exacerbate the risk of MS due to their respective miRNA associations. These findings were then used to determine potential drug candidates through the construction of miRNA-regulated drug-pathway network through genes. We uncovered a total of 48 MS risk pathways, 133 MS risk miRNAs, and 186 drugs that can affect these pathways. Potential MS risk miRNAs that are also regulated by therapeutic candidates were hsa05215 and hsa05152. We analyzed the properties of the miRNA-regulated drug-pathway network through genes and uncovered a number of novel MS agents by assessing their respective Z-values.A total of 20 likely drug candidates were identified, including human immunoglobulin, aspirin, alemtuzumab, minocycline, abciximab, alefacept, palivizumab, bevacizumab, efalizumab, tositumomab, minocycline, etanercept, catumaxomab, and sarilumab. Each of these agents were then explored with regards to their likely mechanism of action in treating MS.The current investigation provides a fresh perspective on MS biological mechanisms as well as likely treatment strategies.Abbreviations: BP = biological processes, CNS = central nervous system, EAE = experimental autoimmune encephalomyelitis, GO = gene ontology, KEGG = Kyoto Encyclopedia of Genes and Genomes, MDNG = miRNA-regulated drug-pathway network through genes, MS = multiple sclerosis, RRMS = remission type multiple sclerosis, SPMS = secondary progressive multiple sclerosis.

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Section: Resultsmentioning

confidence: 99%

Construction of miRNA-regulated drug-pathway network to screen drug repurposing candidates for multiple sclerosis

Kong

Wang²,

Cao³

et al. 2022

Medicine

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“…Akt, functioning as protein kinase B, is a central protein in many cellular pathways such as the cell cycle, growth, survival, metabolism, and immunity. As an isoform, Akt1 has been proved to correlate with autoimmune diseases such as SLE and multiple sclerosis [48,49]. e Akt1/mTOR signaling pathway is crucial for the IL-17 expression [50], which is involved in the pathogenesis of pSS.…”

Section: Discussionmentioning

confidence: 99%

Potential Mechanisms of White Peony against Primary Sjögren’s Syndrome Based on Network Pharmacology and Molecular Docking

Zhuang

Liang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Multiple system and organ damage occurs with the continuous progression of primary Sjögren’s syndrome (pSS), and the lack of specific drugs against this disease is a huge challenge. White peony (WP), a widely used traditional Chinese herb, has been confirmed to have a therapeutic value in pSS. However, the specific mechanisms of WP in the treatment of pSS are unknown. Methods. The active ingredients and their targets in WP were searched on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and disease-related targets were collected from GeneCards, Online Mendelian Inheritance in Man (OMIM), and the Therapeutic Target Database (TTD). The overlapping targets were acquired by taking the intersection. A protein-protein interaction (PPI) network was structured using the STRING database. A disease-drug-ingredient-target (D-D-I-T) network was built using Cytoscape software. By filtering twice, core targets were acquired. Gene Ontology (GO) and Kyoto Encyclopedia Gene and Genome (KEGG) pathway enrichment analysis were accompanied by R packages. Finally, molecular docking was used to verify the abovementioned results. Results. In total, we screened 88 WP-related targets, 1480 pSS-related targets, and 32 overlapping targets. D-D-I-T Network analysis displayed six main active ingredients of WP, which played a significant therapeutic role in pSS. Further topological analysis selected seven core target genes, including IL-6, TNF, PPARγ, AKT1, CASP3, NOS3, and JUN. GO and KEGG analysis were used to elucidate pharmacological mechanisms, mainly acting in the AGE-RAGE signaling pathway. Molecular docking proved that paeoniflorin bound well with core targets. Conclusion. Our study revealed that IL-6, TNF, AKT1, CASP3, NOS3, and JUN may be pathogenic target genes, and PPARγ may be a protective target gene. The main active ingredients of WP mainly played a therapeutic role via the AGE-RAGE signaling pathway. These findings provide a fundamental and theoretical basis for the clinical application of WP.

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“…Interestingly, individuals with the neurodegenerative disorder multiple sclerosis (MS) also are significantly impacted by cognitive loss and dementia (Figure 1). Demyelinating disorders, such as MS, affect a significant proportion of the world's population [38,[126][127][128][129][130][131][132][133][134][135] (Table 1). MS is considered to be the most common demyelinating disorder that affects the immune system and the central nervous system through the function of myelin-producing cells [117,127,134,[136][137][138][139][140].…”

Section: Cognitive Loss and Dementia That Can Occur In Multiple Scler...mentioning

confidence: 99%

Cognitive Impairment in Multiple Sclerosis

Maiese

2023

Bioengineering

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Almost three million individuals suffer from multiple sclerosis (MS) throughout the world, a demyelinating disease in the nervous system with increased prevalence over the last five decades, and is now being recognized as one significant etiology of cognitive loss and dementia. Presently, disease modifying therapies can limit the rate of relapse and potentially reduce brain volume loss in patients with MS, but unfortunately cannot prevent disease progression or the onset of cognitive disability. Innovative strategies are therefore required to address areas of inflammation, immune cell activation, and cell survival that involve novel pathways of programmed cell death, mammalian forkhead transcription factors (FoxOs), the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), and associated pathways with the apolipoprotein E (APOE-ε4) gene and severe acute respiratory syndrome coronavirus (SARS-CoV-2). These pathways are intertwined at multiple levels and can involve metabolic oversight with cellular metabolism dependent upon nicotinamide adenine dinucleotide (NAD+). Insight into the mechanisms of these pathways can provide new avenues of discovery for the therapeutic treatment of dementia and loss in cognition that occurs during MS.

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Expression of Akt1 and p-Akt1 in peripheral T cell subsets of multiple sclerosis patients

Cited by 5 publications

References 17 publications

Construction of miRNA-regulated drug-pathway network to screen drug repurposing candidates for multiple sclerosis

Construction of miRNA-regulated drug-pathway network to screen drug repurposing candidates for multiple sclerosis

Potential Mechanisms of White Peony against Primary Sjögren’s Syndrome Based on Network Pharmacology and Molecular Docking

Cognitive Impairment in Multiple Sclerosis

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