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Expert Opinion on Therapeutic Targets

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https://www.readbyqxmd.com/read/28127991/tshr-as-a-therapeutic-target-in-graves-disease
#1
Terry Smith
Introduction Graves' disease (GD) and thyroid-associated ophthalmopathy (TAO) are thought to result from actions of pathogenic antibodies mediated through the thyrotropin receptor (TSHR). This leads to the unregulated consequences of the antibody-mediated receptor activity in the thyroid and connective tissues of the orbit. Recent studies reveal antibodies that appear to be directed against the insulin-like growth factor-I receptor (IGF-IR). Areas covered In this brief article, I attempt to review the fundamental characteristics of the TSHR, its role in GD and TAO, and its relationship to IGF-IR...
January 27, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28127990/animal-models-suggest-the-trip8b-hcn-interaction-is-a-therapeutic-target-for-major-depressive-disorder
#2
Kyle A Lyman, Ye Han, Dane M Chetkovich
No abstract text is available yet for this article.
January 27, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28081641/vessel-pruning-or-healing-endothelial-metabolism-as-a-novel-target
#3
Anna Rita Cantelmo, Andreas Pircher, Joanna Kalucka, Peter Carmeliet
Antiangiogenic drugs were originally designed to starve tumors by cutting off their vascular supply. Unfortunately, when these agents are used as monotherapy or in combination with chemotherapy, they provide only modest survival benefits in the order of weeks to months in most cancer patients. Strategies normalizing the disorganized tumor vasculature offer the potential to increase tumor perfusion and oxygenation, and to improve the efficacy of radio-, chemo- and immunotherapy, while reducing metastasis. Areas covered: This review discusses tumor vascular normalization (TVN) as an alternative strategy for anti-angiogenic cancer treatment...
January 27, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28092722/synthetic-and-natural-peroxisome-proliferator-activated-receptor-ppar-agonists-as-candidates-for-the-therapy-of-the-metabolic-syndrome
#4
Chek Kun Tan, Yan Zhuang, Walter Wahli
Peroxisome proliferator-activated receptors (PPARs) are the molecular targets of hypolipidemic and insulin-sensitizing drugs and implicated in a multitude of processes that fine-tune the functions of all organs in vertebrates. As transcription factors they sense endogenous and exogenous lipid signaling molecules and convert these signals into intricate gene responses that impact health and disease. The PPARs act as modulators of cellular, organ, and systemic processes, such as lipid and carbohydrate metabolism, making them valuable for understanding body homeostasis influenced by nutrition and exercise...
January 25, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28076698/emerging-role-of-setdb1-as-a-therapeutic-target
#5
Archana Venkataramana Karanth, Radhika Radha Maniswami, Seema Prashanth, Hemalatha Govindaraj, Ramya Padmavathy, Sooriya Kumar Jegatheesan, Ramesh Mullangi, Sriram Rajagopal
Epigenetic changes lead to aberrant gene expression in cancer. SETDB1, a histone lysine methyltransferase plays an important role in methylation and gene silencing. Aberrant histone methylation at H3K9 by SETDB1 promotes silencing of tumor suppressor genes and thus contributes to carcinogenesis. Recent studies indicate that SETDB1 is abnormally expressed in various human cancer conditions which contributed to enhanced tumor growth and metastasis. Hence, SETDB1 appears to be a promising epigenetic target for therapeutic intervention...
January 20, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28081644/reactive-nitrogen-species-as-therapeutic-targets-for-autophagy-implication-for-ischemic-stroke
#6
Jinghan Feng, Xingmiao Chen, Jiangang Shen
Roles of autophagy/mitophagy activation in ischemic stroke remain controversial. To elucidate potential reasons, we analyze the factors responsible for divergent results in literatures. Reactive nitrogen species (RNS) are important cytotoxic factors in ischemic stroke. Herein, we particularly discuss the roles played by RNS in autophagy/mitophagy and ischemic brain injury. Areas covered: Following factors should be considered in the studies on autophagy/mitophagy in ischemic stroke: (1) Protocols for administration of autophagy regulators including administration time points, routes and doses, etc...
January 19, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28064545/androgen-receptor-activation-a-prospective-therapeutic-target-for-bladder-cancer
#7
Taichi Mizushima, Kathleen A Tirador, Hiroshi Miyamoto
Patients with non-muscle-invasive or muscle-invasive bladder cancer undergoing surgery and currently available conventional therapy remain having a high risk of tumor recurrence or progression, respectively. Novel targeted molecular therapy is therefore expected to improve patient outcomes. Meanwhile, substantially higher incidence of bladder cancer in men has prompted research on androgen-mediated androgen receptor (AR) signaling in this malignancy. Indeed, preclinical evidence has suggested that AR signaling plays an important role in urothelial carcinogenesis and tumor outgrowth as well as resistance to some of the currently available conventional non-surgical therapies...
January 19, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28052702/the-potential-of-inhibiting-glutamine-uptake-as-a-therapeutic-target-for-multiple-myeloma
#8
Nicola Giuliani, Martina Chiu, Marina Bolzoni, Fabrizio Accardi, Massimiliano G Bianchi, Denise Toscani, Franco Aversa, Ovidio Bussolati
No abstract text is available yet for this article.
January 18, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28064546/targeting-protein-kinase-b3-akt3-signaling-in-melanoma
#9
SubbaRao V Madhunapantula, Gavin P Robertson
Deregulated Akt activity leading to apoptosis inhibition, enhanced proliferation and drug resistance has been shown to be responsible for 35-70% of advanced metastatic melanomas. Of the three isoforms, the majority of melanomas have elevated Akt3 expression and activity. Hence, potent inhibitors targeting Akt are urgently required, which is possible only if (a) the factors responsible for the failure of Akt inhibitors in clinical trials is known; and (b) the information pertaining to synergistically acting targeted therapeutics is available...
January 16, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28052701/potential-for-targeting-dopamine-darpp-32-signaling-in-neuropsychiatric-and-neurodegenerative-disorders
#10
Akinori Nishi, Takahide Shuto
Alterations in dopamine neurotransmission has been implicated in pathophysiology of neuropsychiatric and neurodegenerative disorders, and DARPP-32 plays a pivotal role in dopamine neurotransmission. DARPP-32 likely influences dopamine-mediated behaviors in animal models of neuropsychiatric and neurodegenerative disorders and therapeutic effects of pharmacological treatment. Areas covered: We will review animal studies on the biochemical and behavioral roles of DARPP-32 in drug addiction, schizophrenia and Parkinson's disease...
January 13, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28055275/the-nr4a-subfamily-of-nuclear-receptors-potential-new-therapeutic-targets-for-the-treatment-of-inflammatory-diseases
#11
Ricardo Rodríguez-Calvo, Marta Tajes, Manuel Vázquez-Carrera
Prolonged inflammatory response contributes to the pathogenesis of chronic disease-related disturbances. Among nuclear receptors (NRs), the orphan NR4A subfamily, which includes Nur77 (NR4A1), Nurr1 (NR4A2) and NOR1 (NR4A3), has recently emerged as a therapeutic target for the treatment of inflammation. Areas covered: This review focuses on the capacity of NR4A receptors to counter-regulate the development of the inflammatory response, with a special focus on the molecular transrepression mechanisms. Expert opinion: Recent studies have highlighted the role of NR4A receptors as significant regulators of the inflammatory response...
January 12, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28019725/the-kcc3-cotransporter-as-a-therapeutic-target-for-peripheral-neuropathy
#12
Eric Delpire, Kristopher T Kahle
No abstract text is available yet for this article.
January 5, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28001437/garp-as-a-therapeutic-target-for-modulation-of-t-regulatory-cell-function
#13
Ethan M Shevach
Foxp3(+) T regulatory cells (Tregs) play critical roles in immune homeostasis primarily by suppressing many aspects of the immune response. Tregs uniquely express GARP on their cell surface and GARP functions as a delivery system for latent TGF-β. As Treg-derived TGF-β may mediate the suppressive functions of Tregs, GARP may represent a target to inhibit Treg suppression in cancer or augment suppression in autoimmunity. Areas covered: This article will focus on 1) the role of Treg-derived TGF-β in the suppressive activity of Treg, 2) the cellular and molecular regulation of expression of GARP on mouse and human Tregs, 3) the role of integrins in the activation of latent-TGF-β/GARP complex, 4) an overview of our present understanding of the function of the latent-TGF-β/GARP complex...
December 29, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28001443/restoring-bmprii-functions-in-pulmonary-arterial-hypertension-opportunities-challenges-and-limitations
#14
Christophe Guignabert, Sabine Bailly, Marc Humbert
Pulmonary arterial hypertension (PAH) is a cardiopulmonary disorder in which mechanical obstruction of the pulmonary vascular bed is largely responsible for the rise in pulmonary arterial pressures. The discovery of heterozygous BMPR2 germline mutations as critical predisposing factors together with a remarkable progress in our understanding of the pathogenic mechanisms have helped identify the significant and complex roles of the BMPRII axis in PAH. However, their precise contributions to the condition are still incompletely understood...
December 28, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28001439/tackling-myocardial-ischemic-injury-the-signal-transducer-and-activator-of-transcription-3-stat3-at-a-good-site
#15
Yang Yang, Wei Hu, Shouyin Di, Zhiqiang Ma, Chongxi Fan, Dongjin Wang, Shuai Jiang, Yue Li, Qing Zhou, Tian Li, Erping Luo
Myocardial ischemia is one of the main causes of cardiac remodeling and heart failure. As a highly evolutionarily conserved pathway, the signal transducer and activator of transcription 3 (STAT3) signaling controls intercellular communication, signaling transduction and gene transcription. Interestingly, STAT3 signaling has been demonstrated to take part in myocardial ischemia. Furthermore, activation of STAT3 signaling contributes to the protective efficacy of various interventions, including pharmacological and non-pharmacological treatment of myocardial ischemic injury...
December 27, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28019723/therapeutical-potential-of-deregulated-lysine-methyltransferase-smyd3-as-a-safe-target-for-novel-anticancer-agents
#16
Gurukumari Rajajeyabalachandran, Swetha Kumar, Thanabal Murugesan, Shanthi Ekambaram, Ramya Padmavathy, Sooriya Kumar Jegatheesan, Ramesh Mullangi, Sriram Rajagopal
SET and MYND domain containing-3 (SMYD3) is a member of the lysine methyltransferase family of proteins, and plays an important role in the methylation of various histone and non-histone targets. Proper functioning of SMYD3 is very important for the target molecules to determine their different roles in chromatin remodeling, signal transduction and cell cycle control. Due to the abnormal expression of SMYD3 in tumors, it is projected as a prognostic marker in various solid cancers. Areas covered: Here we elaborate on the general information, structure and the pathological role of SMYD3 protein...
December 26, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27973928/tyrosine-and-tryptophan-hydroxylases-as-therapeutic-targets-in-human-disease
#17
Kai Waløen, Rune Kleppe, Aurora Martinez, Jan Haavik
The ancient and ubiquitous monoamine signalling molecules serotonin, dopamine, norepinephrine, and epinephrine are involved in multiple physiological functions. The aromatic amino acid hydroxylases tyrosine hydroxylase (TH), tryptophan hydroxylase 1 (TPH1), and tryptophan hydroxylase 2 (TPH2) catalyse the rate-limiting steps in the biosynthesis of these monoamines. Genetic variants of TH, TPH1, and TPH2 genes are associated with neuropsychiatric disorders. The interest in these enzymes as therapeutic targets is increasing as new roles of these monoamines have been discovered, not only in brain function and disease, but also in development, cardiovascular function, energy and bone homeostasis, gastrointestinal motility, hemostasis, and liver function...
December 26, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27936982/mers-cov-spike-protein-a-key-target-for-antivirals
#18
Lanying Du, Yang Yang, Yusen Zhou, Lu Lu, Fang Li, Shibo Jiang
The continual Middle East respiratory syndrome (MERS) threat highlights the importance of developing effective antiviral therapeutics to prevent and treat MERS coronavirus (MERS-CoV) infection. A surface spike (S) protein guides MERS-CoV entry into host cells by binding to cellular receptor dipeptidyl peptidase-4 (DPP4), followed by fusion between virus and host cell membranes. MERS-CoV S protein represents a key target for developing therapeutics to block viral entry and inhibit membrane fusion. Areas covered: This review illustrates MERS-CoV S protein's structure and function, particularly S1 receptor-binding domain (RBD) and S2 heptad repeat 1 (HR1) as therapeutic targets, and summarizes current advancement on developing anti-MERS-CoV therapeutics, focusing on neutralizing monoclonal antibodies (mAbs) and antiviral peptides...
December 21, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27935327/activation-induced-cell-death-aicd-of-human-melanoma-antigen-specific-tcr-engineered-cd8-t-cells-involves-jnk-bim-and-p53
#19
Arvind Chhabra, Bijay Mukherji, Deepika Batra
OBJECTIVES: Adoptive cancer immunotherapy (ACT) with transgenic T cell receptor (TCR) engineered (TCReng) anti-tumor T cells has produced encouraging results, however, efficacy of these approaches need improvement. Since premature activation induced cell death (AICD) of adoptively administered T cells could be a major impediment, we examined the mechanism(s) underlying AICD in TCReng CD8+ cytolytic T lymphocytes (CTL). METHODS: AICD in human tumor antigen-specific MHC class I restricted TCR engineered CD8+ CTL was induced by exposing them to cognate peptide epitope...
December 20, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27978767/clusterin-as-a-therapeutic-target
#20
Mark R Wilson, Amina Zoubeidi
Clusterin (CLU) is a stress-activated, ATP-independent molecular chaperone, normally secreted from cells, that is up-regulated in Alzheimer disease and in many cancers. It plays important roles in protein homeostasis/proteostasis, inhibition of cell death pathways, and modulation of pro-survival signalling and transcriptional networks. Changes in the CLU gene locus are highly associated with Alzheimer disease, and many therapy-resistant cancers over-express CLU. The extensive post-translational processing and heterogeneous oligomerization of CLU have so far prevented any definitive structure determination...
December 16, 2016: Expert Opinion on Therapeutic Targets
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