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Role of Vitamin D and Antioxidant Functional Foods in the Prevention and Treatment of Alzheimer’s Disease Pathology
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
New tools for the study of the molecular pathways affected by this disease include genome-wide association studies and genetic sequencing. Some of the gene families being identified as relevant in disease pathogenesis by these methods include APOE, BIN1, CLU, and CD33. Involved biological pathways include immune response (ABCA7, CD33, CLU, CR1. HLA locus, MEF2C, PTK2B, TREM2), lipid metabolism (ABCA), and endocytosis (BIN1, CD2AP, EPHA1, PICAALM, SORL1) pathways (Verheijen & Sleegers, 2018).
The Role of MAP Kinases, Phosphatidylinositol 3-Kinase, and Ceramide in LPS-induced Signaling in Macrophages
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Anthony L. DeFranco, Alexander J. Finn, Julie Hambleton, Mary T. Crowley, Mary Lee MacKichan, Steven L. Weinstein
Although these three signaling pathways are incompletely understood, a consensus view of the nature of these pathways is shown in Figure 1. Typically, the Erk pathway is activated by Ras and is important for activating transcription from serum-response elements by phosphorylating the Ets family ternary complex factors such as Elk-1. The JNK and p38 pathways may be downstream of another subgroup of low molecular weight GTP-binding proteins, which includes the Rac and CDC42 proteins. JNK and p38 MAP kinase pathways are often activated in cells subjected to stressful conditions such as osmotic shock and hence have also been called stress-activated protein kinases (SAPKs). A major target for JNK is, as the name implies, the bZIP family transcription factor c-Jun. Phosphorylation by JNK of serines 63 and 73 within c-Jun greatly increases its ability to stimulate transcription without affecting its binding to DNA. This promotes gene transcription at AP-1 sites, as can be observed with a reporter gene assay in macrophages stimulated by LPS (22). The p38 MAP kinase can also promote the activity of transcription factors, notably the myocyte enhancer factor MEF2C (31), which may regulate the c-jun promoter. In addition to their ability to act directly on transcription factors, MAP kinases can act on other protein kinases to activate them. For example, in many cell types, Erkl and Erk2 activate p90RSK (27) and p38 activates MAPKAP kinase-2 (32).
Definition, risk factors, and epidemiology of osteoporosis
Published in Peter V. Giannoudis, Thomas A. Einhorn, Surgical and Medical Treatment of Osteoporosis, 2020
New candidates associated with BMD have also been suggested, including wntless Wnt ligand secretion mediator (GPR177) genes, and SRY-box 6 (SOX6), a transcriptional activator that is required for normal development of chondrogenesis and maintenance of skeletal muscle cells (73). A panel of more than 25 genes has been associated with BMD by GWAS analysis in postmenopausal women, including ARHGAP1, CLCN7, CTNNB1, ESR1, FAM3C, FLJ42280, FOXL1, GALNT3, GPR177, HDAC5, IBSP, JAG1, LRP5, LTBP3, MARK3, MEF2C, MEPE, OPG, RANK, RANKL, RSPO3, SOST, SOX4, SOX6, SP7 (Osterix), TARD3NL, and ZBTB40 (74).
Integrated analysis of human transcriptome data for Rett syndrome finds a network of involved genes
Published in The World Journal of Biological Psychiatry, 2020
Friederike Ehrhart, Susan L. Coort, Lars Eijssen, Elisa Cirillo, Eric E. Smeets, Nasim Bahram Sangani, Chris T. Evelo, Leopold M.G. Curfs
Using network extension, we investigated whether there are known transcription factors that may explain the regulation of genes and processes back to their core gene MECP2. Several transcription factors, which were added by network extension, are already known to interact with MECP2: E2F1, MEF2C, REST, SIN3A, SMC3, SP1 and TAF1. E2F1 and TAF1 are promotor elements of MECP2 (Ehrhart et al. 2016). SP1 is known as a cis regulatory element and promotor element of MECP2. REST is a cis regulatory element of MECP2. SIN3A is an integral part of the MECP2-HDAC complex and SMC3 is one of the cofactors of this complex. MEF2C expression is inhibited by MECP2 together with HDAC complex. It interacts with EP300, several histone deacetylases and SP1. Mutations of MEF2C are known to cause mental retardation and psychomotor impairment (Le Meur et al. 2010). Furthermore, the network extension with known transcription factors revealed a possible connection between cytoskeleton organisation and MECP2 via MEF2C and CAPG. We hypothesise that MECP2 regulates CAPG expression via MEF2C (Figure 4).
Single-cell analysis reveals immune modulation and metabolic switch in tumor-draining lymph nodes
Published in OncoImmunology, 2020
Yen-Liang Li, Chung-Hsing Chen, Jing-Yi Chen, You-Syuan Lai, Shao-Chun Wang, Shih-Sheng Jiang, Wen-Chun Hung
The expression profiles of a number of identified DEGs for B cells were shown as in Figures 4c and 4d . Among these DEGs, the transcription factor Mef2c has been shown to be required by B-cell proliferation and survival.44,45 In addition, Mef2c may protect lymphopoiesis of B cells during stress by controlling proper expression of B-cell specific genes.46Sh3bp5 participates in the inhibition of the enzymatic activity of Bruton’s tyrosine kinase, a key regulator in B-cell development.47 Expression of Sh3bp5 was moderately increased in the MMTV-PyMT samples, suggesting that Sh3bp5 may repress the development or maturation of B cells in TDLNs. Genes involved in B cell proliferation and activation were further investigated. It is interesting to note that Cr2, a well-known complement receptor which form a co-receptor on B cells during antigen-induced activation,48 was significantly upregulated; Tgfb1, a potent regulator of B cells development from pre-B cells to immunoglobin secreting plasma cells,49 was significantly down-regulated Figure 4e. Accumulating evidences indicate that secreted tumor products can also influence on distant immunological compartments, including lymphopoiesis. For example, decreased B cell numbers had been reported in tumor-bearing mice.50 Conversely, another study showed that primary tumors induced pro-tumor B cell accumulation in the TDLNs, and B cells promoted lymph-node invasion by producing pathogenic IgG that targeted glycosylated membrane protein HSPA4 to activate downstream pathway in tumor cells to enhance metastasis.51 Although the roles of B cells and their derived antibodies in the formation of pre-metastatic niche are poorly understood, the reprogramming of B cells in TDLNs can be a critical step for lymph-node metastasis.
Impact of clozapine on the expression of miR-675-3p in plasma exosomes derived from patients with schizophrenia
Published in The World Journal of Biological Psychiatry, 2023
Yu Funahashi, Yuta Yoshino, Jun-ichi Iga, Shu-ichi Ueno
The upregulation of hsa-miR-675-3p in the microarray data was successfully replicated in the same samples of patients with TRS by qPCR. Conversely, hsa-miR-675-3p expression was downregulated in the non-TRS group. First, we hypothesised that this opposite result might reflect the different pathophysiologies of TRS and non-TRS because patients with TRS generally show more severe symptoms (Howes et al. 2017), and miRNAs clusters contained in serum EXO have been reported to be correlated with SCZ symptoms (Du et al. 2019); however, hsa-miR-675-3p expression was not correlated with any symptoms in this study. Second, we hypothesised that hsa-miR-675-3p expression was affected by clozapine treatment, which is more effective for TRS compared with other atypical antipsychotics (Nucifora et al. 2017). Actually, in a cell line study, hsa-miR-675-3p upregulation was induced by clozapine treatment in EXO RNA, but not in the total RNA of SH-SY5Y. Amoah et al. (Amoah et al. 2020) reported that antipsychotics (haloperidol and olanzapine) changed the expression of miR-223 in neuronal and astrocytic EXO based on in vivo and in vitro studies. At the functional level of miR-675-3p, two previous studies in the field of cancer reported that miR-675-3p may regulate apoptosis through the regulation of immune-related genes (Li et al. 2020; Shen et al. 2020). Indeed, the predicted target genes of miR-675-3p (e.g. PTRO, SRSF2, CPEB4) have been shown to be relevant to apoptosis (Liang et al. 2017; Shu et al. 2017; Zhu et al. 2020). In addition, MEF2C was predicted as one of the target genes of miR-675-3p. MEF2C, one of the transcription factors in the MEF2 family, has been reported to be a risk gene for SCZ (Harrington et al. 2016), and functional deficits have been found to be associated with cognitive function through epigenetic modification (Mitchell et al. 2018). In addition, MEF2C is relevant to the inflammatory response (Deczkowska et al. 2017) and neuroinflammation (Harrington et al. 2020). When considering the mechanism underlying the effects of clozapine and adverse effects related to immune reactions (Roge et al. 2012), there may be no contradiction in terms of changing miR-675-3p expression levels by clozapine treatment. The H19/IGF2 imprinted domain on chromosome 11 contains miR-675 matured from the H19 transcript expressed from the maternal chromosome (Girardot et al. 2012). Because hsa-miR-675-3p is located in this imprinted region, this miRNA might be associated with parent of origin (Gardiner et al. 2012). However, as far as we know, precise abnormal imprinting mechanisms of this miRNA remain unknown.