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Signaling pathways AND Review

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https://www.readbyqxmd.com/read/28335551/molecular-basis-for-modulation-of-metabotropic-glutamate-receptors-and-their-drug-actions-by-extracellular-ca-2
#1
REVIEW
Juan Zou, Jason Y Jiang, Jenny J Yang
Metabotropic glutamate receptors (mGluRs) associated with the slow phase of the glutamatergic signaling pathway in neurons of the central nervous system have gained importance as drug targets for chronic neurodegenerative diseases. While extracellular Ca(2+) was reported to exhibit direct activation and modulation via an allosteric site, the identification of those binding sites was challenged by weak binding. Herein, we review the discovery of extracellular Ca(2+) in regulation of mGluRs, summarize the recent developments in probing Ca(2+) binding and its co-regulation of the receptor based on structural and biochemical analysis, and discuss the molecular basis for Ca(2+) to regulate various classes of drug action as well as its importance as an allosteric modulator in mGluRs...
March 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28335463/dysfunctional-mtorc1-signaling-a-convergent-mechanism-between-syndromic-and-nonsyndromic-forms-of-autism-spectrum-disorder
#2
REVIEW
Juliana Magdalon, Sandra M Sánchez-Sánchez, Karina Griesi-Oliveira, Andréa L Sertié
Whereas autism spectrum disorder (ASD) exhibits striking heterogeneity in genetics and clinical presentation, dysfunction of mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway has been identified as a molecular feature common to several well-characterized syndromes with high prevalence of ASD. Additionally, recent findings have also implicated mTORC1 signaling abnormalities in a subset of nonsyndromic ASD, suggesting that defective mTORC1 pathway may be a potential converging mechanism in ASD pathology across different etiologies...
March 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28334198/molecular-mechanisms-involved-in-the-interaction-of-neisseria-meningitidis-with-cells-of-the-human-blood-cerebrospinal-fluid-barrier
#3
Alexandra Schubert-Unkmeir
Neisseria meningitidis is one of the most common aetiological agents of bacterial meningitis, affecting predominantly children and young adults. The interaction of N. meningitidis with human endothelial cells lining blood vessels of the blood-cerebrospinal-fluid barrier (B-CSFB) is critical for meningitis development. In recent decades, there has been a significant increase in understanding of the molecular mechanisms involved in the interaction of N. meningitidis with brain vascular cells. In this review, we will describe how N...
March 3, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28334065/an-overview-of-mechanisms-of-cry-toxin-resistance-in-lepidopteran-insects
#4
B Peterson, C C Bezuidenhout, J Van den Berg
Arthropods have the capacity to evolve resistance to insecticides and insecticidal traits in genetically modified crops. Resistance development among Lepidoptera is a common phenomenon, and a repertoire of resistance mechanisms to various Cry toxins have been identified from laboratory, greenhouse, and field studies in this insect order. Elucidation of such resistance mechanisms is crucial for developing IRM (insect resistance management) strategies to ensure sustainable use of genetically modified crops. This mini review provides a comprehensive overview of mechanisms of resistance that have been reported for lepidopteran pests...
February 16, 2017: Journal of Economic Entomology
https://www.readbyqxmd.com/read/28333382/regulation-and-function-of-extracellular-nicotinamide-phosphoribosyltransferase-visfatin
#5
Federico Carbone, Luca Liberale, Aldo Bonaventura, Alessandra Vecchiè, Matteo Casula, Michele Cea, Fiammetta Monacelli, Irene Caffa, Santina Bruzzone, Fabrizio Montecucco, Alessio Nencioni
Nicotinamide phosphoribosyltransferase (NAMPT) is an adipokine-enzyme, which was described as to play bioactivities both in the intracellular and in the extracellular environment. However, while the functions of intracellular NAMPT (iNAMPT) are well known, much less is known on extracellular NAMPT (eNAMPT), also called visfatin or pre-B cell colony-enhancing factor. iNAMPT catalyzes the rate-limiting step in the NAD+ biosynthesis pathway from nicotinamide. Its inhibition severely reduces intracellular NAD+ levels, achieving anti-inflammatory and anti-cancer effects...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28333381/protective-actions-of-h2s-in-acute-myocardial-infarction-and-heart-failure
#6
Erminia Donnarumma, Rishi K Trivedi, David J Lefer
Hydrogen sulfide (H2S) was identified as the third gasotransmitter in 1996 following the discoveries of the biological importance of nitric oxide and carbon monoxide. Although H2S has long been considered a highly toxic gas, the discovery of its presence and enzymatic production in mammalian tissues supports a critical role for this physiological signaling molecule. H2S is synthesized endogenously by three enzymes: cystathionine β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase. H2S plays a pivotal role in the regulation of cardiovascular function as H2S has been shown to modulate: vasodilation, angiogenesis, inflammation, oxidative stress, and apoptosis...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28331908/il-1%C3%AE-is-an-innate-immune-sensor-of-microbial-proteolysis
#7
Christopher N LaRock, Jordan Todd, Doris L LaRock, Joshua Olson, Anthony J O'Donoghue, Avril A B Robertson, Matthew A Cooper, Hal M Hoffman, Victor Nizet
Interleukin-1β (IL-1β) is a key proinflammatory cytokine that drives antimicrobial immune responses. IL-1β is aberrantly activated in autoimmune diseases, and IL-1β inhibitors are used as therapeutic agents to treat patients with certain autoimmune disorders. Review of postmarketing surveillance of patients receiving IL-1β inhibitors found a disproportionate reporting of invasive infections by group A Streptococcus (GAS). IL-1β inhibition increased mouse susceptibility to GAS infection, but IL-1β was produced independent of canonical inflammasomes...
August 2016: Science Immunology
https://www.readbyqxmd.com/read/28331574/microrna-and-thyroid-hormone-signaling-in-cardiac-and-skeletal-muscle
#8
REVIEW
Duo Zhang, Yan Li, Shengnan Liu, Yu-Cheng Wang, Feifan Guo, Qiwei Zhai, Jingjing Jiang, Hao Ying
Thyroid hormone (TH) signaling plays critical roles in the differentiation, growth, metabolism, and physiological function of all organs or tissues, including heart and skeletal muscle. Due to the significant progress in our understanding of the molecular mechanisms that underlie TH action, it's widely accepted that TH signaling is regulated at multiple levels. A growing number of discoveries suggest that microRNAs (miRNAs) act as fine-tune regulators of gene expression and adds sophisticated regulatory tiers to signaling pathways...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28331572/environmental-risk-factors-for-autism-an-evidence-based-review-of-systematic-reviews-and-meta-analyses
#9
REVIEW
Amirhossein Modabbernia, Eva Velthorst, Abraham Reichenberg
BACKGROUND: According to recent evidence, up to 40-50% of variance in autism spectrum disorder (ASD) liability might be determined by environmental factors. In the present paper, we conducted a review of systematic reviews and meta-analyses of environmental risk factors for ASD. We assessed each review for quality of evidence and provided a brief overview of putative mechanisms of environmental risk factors for ASD. FINDINGS: Current evidence suggests that several environmental factors including vaccination, maternal smoking, thimerosal exposure, and most likely assisted reproductive technologies are unrelated to risk of ASD...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28330758/regulation-of-type-i-interferon-signaling-in-immunity-and-inflammation-a-comprehensive-review
#10
REVIEW
Kun Chen, Juan Liu, Xuetao Cao
Type I interferons (IFNs) play essential roles in establishing and modulating host defense against microbial infection via induction of IFN-stimulated genes (ISGs) through Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. However, dysregulation of IFNs production and function could also mediate immune pathogenesis such as inflammatory autoimmune diseases and infectious diseases via aberrantly activating inflammatory responses or improperly suppressing microbial controls...
March 19, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28330703/mitogen-activated-protein-kinase-phosphatase-1-mkp-1-in-macrophage-biology-and-cardiovascular-disease-a-redox-regulated-master-controller-of-monocyte-function-and-macrophage-phenotype
#11
REVIEW
Hong Seok Kim, Reto Asmis
MAPK pathways play a critical role in the activation of monocytes and macrophages by pathogens, signaling molecules and environmental cues and in the regulation of macrophage function and plasticity. MAPK phosphatase 1 (MKP-1) has emerged as the main counter-regulator of MAPK signaling in monocytes and macrophages. Loss of MKP-1 in monocytes and macrophages in response to metabolic stress leads to dysregulation of monocyte adhesion and migration, and gives rise to dysfunctional, proatherogenic monocyte-derived macrophages...
March 18, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28328745/gpcr-signaling-via-%C3%AE-arrestin-dependent-mechanisms
#12
Pierre-Yves Jean-Charles, Suneet Kaur, Sudha K Shenoy
β-arrestin1 (or arrestin2) and β-arrestin2 (or arrestin3) are ubiquitously expressed cytosolic adaptor proteins that were originally discovered for their inhibitory role in G protein-coupled receptor (GPCR) signaling via heterotrimeric G proteins. However, further biochemical characterization revealed that β-arrestins do not just 'block' the activated GPCRs, but trigger endocytosis and kinase activation leading to specific signaling pathways that can be localized on endosomes. The signaling pathways initiated by β-arrestins were also found to be independent of G protein activation by GPCRs...
March 17, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28328290/cross-talk-between-rho-gtpases-and-pi3k-in-the-neutrophil
#13
Barry McCormick, Julia Y Chu, Sonja Vermeren
Neutrophils are short-lived, abundant peripheral blood leukocytes that provide a first line of defense against bacterial and fungal infections whilst also being a key part of the inflammatory response. Chemokines induce neutrophil recruitment to inflammatory sites, where neutrophils perform a number of diverse functions that are aimed at fighting infections. Neutrophil effector functions are tightly regulated processes that are governed by an array of intracellular signaling pathways and initiated by receptor-ligand binding events...
March 22, 2017: Small GTPases
https://www.readbyqxmd.com/read/28328117/noonan-syndrome-ptpn11-mutations-and-brain-tumors-a-clinical-report-and-review-of-the-literature
#14
Aurore Siegfried, Claude Cances, Marie Denuelle, Najat Loukh, Maïté Tauber, Hélène Cavé, Marie-Bernadette Delisle
Noonan syndrome (NS), an autosomal dominant disorder, is characterized by short stature, congenital heart defects, developmental delay, and facial dysmorphism. PTPN11 mutations are the most common cause of NS. PTPN11 encodes a non-receptor protein tyrosine phosphatase, SHP2. Hematopoietic malignancies and solid tumors are associated with NS. Among solid tumors, brain tumors have been described in children and young adults but remain rather rare. We report a 16-year-old boy with PTPN11-related NS who, at the age of 12, was incidentally found to have a left temporal lobe brain tumor and a cystic lesion in the right thalamus...
April 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28326864/role-of-the-notch-signaling-in-cholangiocarcinoma
#15
Antonio Cigliano, Jingxiao Wang, Xin Chen, Diego F Calvisi
Cholangiocarcinoma (CCA) is an emerging cancer entity of the liver, associated with poor outcome and characterized by resistance to conventional chemotherapeutic treatments. In the last decade, many signaling pathways associated with CCA development and progression have been identified and are currently under intense investigation. Cumulating evidence indicates that the Notch cascade, a highly-conserved pathway in most multicellular organisms, is a critical player both in liver malignant transformation and tumor aggressiveness, thus representing a potential therapeutic target in this pernicious disease...
March 22, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28326543/animal-models-for-studying-motor-axon-terminal-paralysis-and-recovery
#16
REVIEW
Michela Rigoni, Cesare Montecucco
An extraordinary property of the peripheral nervous system is that nerve terminals can regenerate after damage caused by different physical, chemical, or biological pathogens. Regeneration is the result of a complex and ill-known interplay among the nerve, the glia, the muscle, the basal lamina and, in some cases, the immune system. This phenomenon has been studied using different injury models mainly in rodents, particularly in mice, where a lesion can be produced in a chosen anatomical area. These approaches differ significantly among them for the nature of the lesion and the final outcomes...
March 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28325816/papers-of-note-in-science355-6330
#17
Annalisa M VanHook
This week's articles include several reviews on targeting signaling pathways to treat cancer, as well as research articles that highlight proteins that drive circadian clocks; how bacteriophages affect the virulence of pathogenic bacteria; a mobile transcription factor in plants; a secreted nucleoside that affects metabolism; and the effects of protein aggregation in aging yeast cells.
March 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28325629/towards-integrating-extracellular-matrix-and-immunological-pathways
#18
David F Boyd, Paul G Thomas
The extracellular matrix (ECM) is a complex and dynamic structure made up of an estimated 300 different proteins. The ECM is also a rich source of cytokines and growth factors in addition to numerous bioactive ECM degradation products that influence cell migration, proliferation, and differentiation. The ECM is constantly being remodeled during homeostasis and in a wide range of pathological contexts. Changes in the ECM modulate immune responses, which in turn regulate repair and regeneration of tissues. Here, we review the many components of the ECM, enzymes involved in ECM remodeling, and the signals that feed into immunological pathways in the context of a dynamic ECM...
March 18, 2017: Cytokine
https://www.readbyqxmd.com/read/28325280/mir-134-a-human-cancer-suppressor
#19
REVIEW
Jing-Yu Pan, Feng Zhang, Cheng-Cao Sun, Shu-Jun Li, Guang Li, Feng-Yun Gong, Tao Bo, Jing He, Rui-Xi Hua, Wei-Dong Hu, Zhan-Peng Yuan, Xin Wang, Qi-Qiang He, De-Jia Li
MicroRNAs (miRNAs) are small noncoding RNAs approximately 20-25 nt in length, which play crucial roles through directly binding to corresponding 3' UTR of targeted mRNAs. It has been reported that miRNAs are involved in numerous of diseases, including cancers. Recently, miR-134 has been identified to dysregulate in handles of human cancers, such as lung cancer, glioma, breast cancer, colorectal cancer, and so on. Increasing evidence indicates that miR-134 is essential for human carcinoma and participates in tumor cell proliferation, apoptosis, invasion and metastasis, drug resistance, as well as cancer diagnosis, treatment, and prognosis...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28325267/enzastaurin-a-lesson-in-drug-development
#20
REVIEW
T Bourhill, A Narendran, R N Johnston
Enzastaurin is an orally administered drug that was intended for the treatment of solid and haematological cancers. It was initially developed as an isozyme specific inhibitor of protein kinase Cβ (PKCβ), which is involved in both the AKT and MAPK signalling pathways that are active in many cancers. Enzastaurin had shown encouraging preclinical results for the prevention of angiogenesis, inhibition of proliferation and induction of apoptosis as well as showing limited cytotoxicity within phase I clinical trials...
April 2017: Critical Reviews in Oncology/hematology
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