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Expert Opinion on Therapeutic Targets

Bing Han, Louis M Weiss
Microsporidia have been increasingly reported to infect humans. The most common presentation of microsporidia infection is chronic diarrhea which can be extremely debilitating and carries a significant mortality risk in immune compromised patients. Albendazole, which inhibits tubulin, and fumagillin, which inhibits methionine aminopeptidase type 2 (MetAP2), are currently the two main therapeutic agents used for microsporidiosis treatment. In addition, to their role as emerging pathogens in humans, the Microsporidia are important pathogens in commercially important insects, aquaculture, and veterinary medicine...
October 19, 2018: Expert Opinion on Therapeutic Targets
Yoon Jin Cha, Ja Seung Koo
Adipocytes, which represent a substantial part of the tumor microenvironment in breast cancer, secrete several adipokines that affect tumorigenesis, cancer progression, metastasis and treatment resistance via multiple signaling pathways. Areas covered: In this review, we focus on the role of leptin, adiponectin, autotaxin and interleukin-6 in breast cancer initiation, progression, metastasis and drug response. Furthermore, we investigated adipokines as potential targets of breast cancer-specific drugs. Expert opinion: Adipokines and adipokine receptors are deregulated in breast cancer...
October 17, 2018: Expert Opinion on Therapeutic Targets
Liang Wang, Imad Shureiqi, John R Stroehlein, Daoyan Wei
No abstract text is available yet for this article.
October 17, 2018: Expert Opinion on Therapeutic Targets
Maud-Emmanuelle Gilles, Frank J Slack
MicroRNAs (miRNA) are a class of small non-coding RNA that play a major role in various cellular processes by negatively regulating gene expression. In the past decade, miRNA dysregulation has been reported to be closely linked to inflammatory diseases. The immune response modulates cancer initiation and progression; miRNAs including let-7 family members have been shown to act as key regulators of the immune responses in various diseases and cancers. Notably, the let-7 miRNA has been reported to be closely associated with immunity, specifically with Toll-like receptors that mediate cytokine expression during pathogen infection and with the regulation of various other immune effectors...
October 17, 2018: Expert Opinion on Therapeutic Targets
David B Sykes
No abstract text is available yet for this article.
October 13, 2018: Expert Opinion on Therapeutic Targets
Timo Uphaus, Frauke Zipp, Catherine Larochelle
No abstract text is available yet for this article.
October 12, 2018: Expert Opinion on Therapeutic Targets
F David Carmona, Javier Martín Ibáñez
PTPN22 encodes a lymphoid-specific tyrosine phosphatase (LYP) that is a master regulator of the immune response. This gene is a major susceptibility factor for a wide range of autoimmune conditions, including rheumatoid arthritis (RA) for which it represents the strongest non-HLA contributor to disease risk. A missense PTPN22 allele (R620W) affecting the protein-protein interaction of LYP with other relevant players was described as the functional variant of the association. This review will focus on the role of PTPN22 in the pathogenic mechanisms underlying RA predisposition and discuss the possibility of developing LYP-based treatment strategies with a potential application in clinical practice...
September 25, 2018: Expert Opinion on Therapeutic Targets
Yoshihiro Ito, Jonathan R Hart, Peter K Vogt
The main regulatory subunits of Class IA phosphatidylinositol 3-kinase (PI3K), p85α and p85β, initiate diverse cellular activities independent of binding to the catalytic subunit p110. Several of these signaling processes directly or indirectly contribute to a regulation of PI3K and could become targets for therapeutic efforts. Areas covered: This review will highlight two general areas of p85 activity: (1) direct interaction with regulatory proteins and with determinants of the cytoskeleton, and (2) a genetic analysis by deletion and domain switches identifying new functions for p85 domains...
September 24, 2018: Expert Opinion on Therapeutic Targets
Wenting Du, Rolf A Brekken
Pancreatic cancer is a leading cause of cancer-related death. Metastasis, therapy resistance, and immunosuppression are dominant characteristics of pancreatic tumors. Strategies that enhance the efficacy of standard of care and/or immune therapy are likely the most efficient route to improve overall survival in this disease. Areas covered: Axl, a member of the TAM (Tyro3, Axl, MerTK) family of receptor tyrosine kinases, is involved in cell plasticity, chemoresistance, immune suppression, and metastasis in various cancers, including pancreatic cancer...
September 23, 2018: Expert Opinion on Therapeutic Targets
Przemysław Duda, Janusz Wiśniewski, Tomasz Wójtowicz, Olga Wójcicka, Michał Jaśkiewicz, Dominika Drulis-Fajdasz, Dariusz Rakus, James A McCubrey, Agnieszka Gizak
Glycogen synthase kinase 3 (GSK3) is at the center of cellular signaling and controls various aspects of brain functions, including development of the nervous system, neuronal plasticity and onset of neurodegenerative disorders. Areas covered: In this review, recent efforts in elucidating the roles of GSK3 in neuronal plasticity and development of brain pathologies; Alzheimer's and Parkinson's disease, schizophrenia, and age-related neurodegeneration are described. The effect of microglia and astrocytes on development of the pathological states is also discussed...
September 22, 2018: Expert Opinion on Therapeutic Targets
Petra Zimmermann, Nigel Curtis
Aspirin (acetylsalicylic acid, ASA) is a commonly used drug that is often co-administered during the treatment of infections. Salicylic acid (SAL), the active metabolite of ASA, has significant effects on bacteria that might improve or (more likely) compromise the effectiveness of antibiotics. Areas covered: In this review, we summarise the interactions between SAL and antibiotics and the underlying mechanisms involved. Expert opinion: In an era of rapidly increasing antibiotic resistance and a lack of new antibiotic development, it is important to explore ways to optimise the effectiveness of antimicrobial treatment...
September 22, 2018: Expert Opinion on Therapeutic Targets
Radhika Sharma, Karan Razdan, Yashika Bansal, Anurag Kuhad
Alzheimer's disease (AD) is associated with cerebral cognitive deficits exhibiting two cardinal hallmarks: accruement of extracellular amyloid plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. The currently accessible therapeutic armamentarium merely provides symptomatic relief. Therefore, the cry for prospective neuroprotective strategies seems to be the need of the hour. Areas covered: This review comprehensively establishes correlation between kynurenine pathway (KP) metabolites and AD with major emphasis on its two functionally contrasting neuroactive metabolites i...
September 18, 2018: Expert Opinion on Therapeutic Targets
Philip Campbell, Huw Morris, Anthony Schapira
Parkinson disease (PD) is the most common neurodegenerative movement disorder. Currently only symptomatic treatments exist for PD, and so the search for potential neuroprotective drug targets is of great importance. Chaperone mediated autophagy (CMA) is one of the key cellular mechanisms in protein homeostasis. Many of the pathogenic pathways thought to be important in PD converge on CMA, thus rendering it an attractive therapeutic target. Areas covered: In this review we discuss current up-to-date knowledge of the molecular mechanisms involved in CMA function and regulation...
September 10, 2018: Expert Opinion on Therapeutic Targets
Neelima Gupta, Sukanya Shyamasundar, Radhika Patnala, Aparna Karthikeyan, Thiruma V Arumugam, Eng-Ang Ling, S Thameem Dheen
Chronic activation of microglia is the hallmark of numerous neuropathologies such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. The activated microglia perpetuate inflammation by releasing an array of pro-inflammatory and neurotoxic factors, which eventually exacerbate neurotoxicity and neurodegeneration upon chronic activation of these cells. However, under acute conditions, activated microglia elicit pro-inflammatory as well as anti-inflammatory responses that are associated with neuroprotection...
September 10, 2018: Expert Opinion on Therapeutic Targets
Nuozhou Wang, Shanshan Wang, Sheng-Li Yang, Li-Ping Liu, Ming-Yue Li, Paul B S Lai, George G Chen
Zinc-binding protein-89 (ZBP-89) is a Krüppel-type zinc-finger transcription factor that regulates target gene expression profiles via directly binding to GC-rich gene promoters, recruiting chromatin modifiers or by interacting with other proteins. The importance of ZBP-89 in the regulation of cell cycle arrest and apoptosis has led to increased interest and investigations for its role in cancer development. Areas covered: We describe ZBP-89 as a candidate therapeutic target for hepatocellular carcinoma (HCC) from several perspectives...
September 6, 2018: Expert Opinion on Therapeutic Targets
Jason Tasoulas, Gerasimos Tsourouflis, Stamatios Theocharis
Neovascularization in carcinogenesis and tumor progression is well-established. Molecular mediators implicated in different modes of vascular remodeling and expansion (e.g. sprouting angiogenesis (SA), vasculogenesis, vascular mimicry) are evaluated as prognostic biomarkers and therapeutic targets in different malignant tumors. Significant progress has been made in the understanding of the complex interplay between thyroid cancer (TC) cells and the tumor microenvironment, thus unraveling the role of angiogenic mediators...
September 2018: Expert Opinion on Therapeutic Targets
Jakub Rosik, Bartosz Szostak, Filip Machaj, Andrzej Pawlik
INTRODUCTION: Heart failure (HF) is one of the most prevalent diseases; it affects millions of people every year. In addition to being one of the major causes of mortality, it generates a financial burden on healthcare systems. Despite progress in developing new pharmaceuticals intended to treat HF, even the newest therapies are not satisfactory. Ischemic heart disease often requires operational treatment which decreases the patient's quality of life. The emergence of gene therapy as a viable treatment option for monogenic disorders has resulted in the approach becoming a topic of study in cardiology...
September 2018: Expert Opinion on Therapeutic Targets
Daniela Loessner, Peter Goettig, Sarah Preis, Johanna Felber, Holger Bronger, Judith A Clements, Julia Dorn, Viktor Magdolen
Aberrant levels of kallikrein-related peptidases (KLK1-15) have been linked to cancer cell proliferation, invasion and metastasis. In ovarian cancer, the KLK proteolytic network has a crucial role in the tissue and tumor microenvironment. Publically available ovarian cancer genome and expression data from multiple patient cohorts show an upregulation of most KLKs. Areas covered: Here, we review the expression levels of all 15 members of this family in normal and ovarian cancer tissues, categorizing them into highly and moderately or weakly expressed KLKs, and their association with patient prognosis and survival...
September 2018: Expert Opinion on Therapeutic Targets
Carlo Riccardi, Simona Ronchetti, Giuseppe Nocentini
Triggering of the glucocorticoid-induced TNFR-related gene (GITR) increases the activation of T lymphocytes and other immune system cells; furthermore, its ligand, GITRL, delivers signals in the cells where it is expressed. Areas covered: This review describes the effects of GITR/GITRL triggering/inhibition in conventional T cells, regulatory T cells (Tregs), monocytes/macrophages, endothelial cells and other cells of the immune system. GITR triggering appears to be an approach for promoting tumor rejection, treating infection and boosting vaccinations in several murine models...
September 2018: Expert Opinion on Therapeutic Targets
Valentina Pucino, Danilo Cucchi, Claudio Mauro
Inflammation is associated with the accumulation of lactate at sites of tumor-growth and inflammation. Lactate initiates tissue-responses contributing to disease. We discuss the potential of targeting lactate transporters in the treatment of cancer and inflammatory conditions. Areas covered: Lactate is the end product of glycolysis, often considered a waste metabolite but also a fuel for oxidative cells. It is however an active signaling molecule with immunomodulatory and angiogenic properties. They are the consequence of lactate binding to membrane receptor(s) or being transported through specific carrier-mediated-transporters across the cellular membrane...
September 2018: Expert Opinion on Therapeutic Targets
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