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Expert Opinion on Therapeutic Targets

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https://www.readbyqxmd.com/read/28434268/ubiquitin-c-terminal-hydrolase-l1-uch-l1-as-a-therapeutic-and-diagnostic-target-in-neurodegeneration-neurotrauma-and-neuro-injuries
#1
Kevin K Wang, Zhihui Yang, George Sarkis, Isabel Torres, Vijaya Raghavan
Since its discovery as a major CNS-abundant protein 25 years ago, Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has emerged as an important enzyme in regulating brain protein metabolism, by coupling to the proteasome pathway of protein degradation. Areas covered: UCH-L1 is implicated in both familial and sporadic Parkinson disease and other chronic neurodegenerative diseases. Also, UCH-L1 has been recently emerging as a biofluid-based biomarker for various forms of acute neurotrauma and CNS injury. Expert opinion: The loss of UCH-L1 activity coupled with the gain of proteinopathy function are linked to neurodegeneration such as Parkinsonism and Alzheimer's disease...
April 24, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28434262/the-emergence-of-acid-ceramidase-as-a-therapeutic-target-for-acute-myeloid-leukemia
#2
Su-Fern Tan, Jennifer M Pearson, David J Feith, Thomas P Loughran
Acute myeloid leukemia (AML) is the most common adult leukemia. Only a fraction of AML patients will survive with existing chemotherapy regimens. Hence, there is an urgent and unmet need to identify novel targets and develop better therapeutics in AML. In the past decade, the field of sphingolipid metabolism has emerged into the forefront of cancer biology due to its importance in cancer cell proliferation and survival. In particular, acid ceramidase (AC) has emerged as a promising therapeutic target due to its role in neutralizing the pro-death effects of ceramide...
April 24, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28406715/competitive-endogenous-rna-network-potential-implication-for-systemic-lupus-erythematosus
#3
Lian-Ju Li, Wei Zhao, Sha-Sha Tao, Rui-Xue Leng, Yin-Guang Fan, Hai-Feng Pan, Dong-Qing Ye
Competitive endogenous RNA (ceRNA) hypothesis proposes that RNA transcripts, both coding and non-coding, crosstalk with and coregulate each other using microRNA response elements (MREs). CeRNA analysis tremendously expands functional information of coding and non-coding RNAs. Mounting evidence have shown that various types of RNAs, including pseudogenes, long non-coding RNAs, circular RNAs, and messenger RNAs, can function as ceRNAs in distinct physiological and pathophysiological states. Many validated ceRNA pairs participate in the initiation and progression of cancers, and systemic ceRNA network analyses revealing potential of ceRNAs in diagnosis, therapy, and prognosis of cancers have also been performed...
April 23, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28406046/depdc5-as-a-potential-therapeutic-target-for-epilepsy
#4
Kenneth A Myers, Ingrid E Scheffer
Dishevelled, Egl-10 and Pleckstrin (DEP) domain-containing protein 5 (DEPDC5) is a protein subunit of the GTPase-activating proteins towards Rags 1 (GATOR1) complex. GATOR1 is a recently identified modulator of mechanistic target of rapamycin (mTOR) activity. mTOR is a key regulator of cell proliferation and metabolism; disruption of the mTOR pathway is implicated in focal epilepsy, both acquired and genetic. Tuberous sclerosis is the prototypic mTOR genetic syndrome with epilepsy, however GATOR1 gene mutations have recently been shown to cause lesional and non-lesional focal epilepsy...
April 13, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28395542/targetting-ped-pea-15-for-diabetes-treatment
#5
Francesca Fiory, Rosa Spinelli, Gregory Alexander Raciti, Luca Parrillo, Vittoria D'Esposito, Pietro Formisano, Claudia Miele, Francesco Beguinot
PED/PEA-15 is an ubiquitously expressed protein, involved in the regulation of proliferation and apoptosis. It is commonly overexpressed in Type 2 Diabetes (T2D) and in different T2D-associated comorbidities, including cancer and certain neurodegenerative disorders. Areas covered: In mice, Ped/Pea-15 overexpression impairs glucose tolerance and, in combination with high fat diets, further promotes insulin resistance and T2D. It also controls β-cell mass, altering caspase-3 activation and the expression of pro- and antiapoptotic genes...
April 11, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28333549/ksr-as-a-therapeutic-target-for-ras-dependent-cancers
#6
Beth K Neilsen, Danielle E Frodyma, Robert E Lewis, Kurt W Fisher
Targeting downstream effectors required for oncogenic Ras signaling is a potential alternative or complement to the development of more direct approaches targeting Ras in the treatment of Ras-dependent cancers. Areas covered: Here we review literature pertaining to the molecular scaffold Kinase Suppressor of Ras (KSR) and its role in promoting signals critical to tumor maintenance. We summarize the phenotypes in knockout models, describe the role of KSR in cancer, and outline the structure and function of the KSR1 and KSR2 proteins...
April 7, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28372474/corrigendum
#7
(no author information available yet)
No abstract text is available yet for this article.
April 3, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28338377/sodium-potassium-adenosine-triphosphatase-na-k-atpase-as-a-therapeutic-target-for-uremic-cardiomyopathy
#8
Xiaoliang Wang, Jiang Liu, Christopher A Drummond, Joseph I Shapiro
Clinically, patients with significant reductions in renal function present with cardiovascular dysfunction typically termed, uremic cardiomyopathy. It is a progressive series of cardiac pathophysiological changes, including left ventricular diastolic dysfunction and hypertrophy (LVH) which sometimes progress to left ventricular dilation (LVD) and systolic dysfunction in the setting of chronic kidney disease (CKD). Uremic cardiomyopathy is almost ubiquitous in patients afflicted with end stage renal disease (ESRD)...
April 3, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28338356/the-accessory-gene-regulator-1-as-a-therapeutic-target-for-c-difficile-infections
#9
Charles Darkoh, Herbert L DuPont
No abstract text is available yet for this article.
April 3, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28335655/the-therapeutic-potential-of-targeting-abc-transporters-to-combat-multi-drug-resistance
#10
Piyush Bugde, Riya Biswas, Fabrice Merien, Jun Lu, Dong-Xu Liu, Mingwei Chen, Shufeng Zhou, Yan Li
Most disseminated cancers remain fatal despite the availability of a variety of conventional and novel treatments including surgery, chemotherapy, radiotherapy, immunotherapy, and biologically targeted therapy. A major factor responsible for the failure of chemotherapy in the treatment of cancer is the development of multidrug resistance (MDR). The overexpression of various ABC transporters in cancer cells can efficiently remove the anticancer drug from the cell, thus causing the drug to lose its effect. Areas covered: In this review, we summarised the ongoing research related to the mechanism, function, and regulation of ABC transporters...
April 3, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28338370/the-potential-of-stimulating-nitric-oxide-formation-in-the-treatment-of-hypertension
#11
Lucas C Pinheiro, Jose E Tanus-Santos, Michele M Castro
Hypertension is a leading cause of morbidity and mortality worldwide. A major pathophysiological factor contributing to hypertension is reduced nitric oxide (NO) bioavailability. Strategies to address this pathophysiological mechanism could offer significant advantages. Areas covered: In this review we aimed at examining a variety of drugs (statins, beta-adrenergic receptor blockers, calcium channel blockers, angiotensin converting enzyme inhibitors, angiotensin II type-1 receptor blockers) used to treat hypertension and other cardiovascular diseases, particularly with respect to their potential of increasing NO bioavailability and activity in the cardiovascular system...
March 30, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28326864/role-of-the-notch-signaling-in-cholangiocarcinoma
#12
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 30, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28323497/potential-mechanisms-underlying-cdk5-related-osteosarcoma-progression
#13
Hang-Xing Bao, Qing Bi, Yong Han, Chen Zhao, Hai Zou
OBJECTIVES: Identification of new prognostic biomarkers and therapeutic targets is of crucial importance for patients with osteosarcoma. Cyclin-dependent kinase 5 (CDK5) is overexpressed in several tumor types. However, the exact role CDK5 plays in osteosarcoma is still unknown. METHODS: In this study, we explored the association between CDK5 expression and the prognosis of osteosarcoma patients using publicly available gene expression datasets. Potential molecular mechanisms underlying its pro-malignant role in cancer progression were also discussed...
March 28, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28332852/corrigendum
#14
(no author information available yet)
No abstract text is available yet for this article.
March 23, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28317405/corrigendum
#15
(no author information available yet)
No abstract text is available yet for this article.
March 20, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28282502/signaling-pathways-as-therapeutic-targets-in-biliary-tract-cancer
#16
Jennifer Yang, Matthew R Farren, Daniel Ahn, Tanios Bekaii-Saab, Gregory B Lesinski
The incidence of biliary tract cancer (BTC) is increasing, and the disease is frequently diagnosed during advanced stages, leading to poor overall survival. Limited treatment options are currently available and novel therapeutic approaches are needed. A number of completed clinical trials have evaluated the role of chemotherapy for BTC, demonstrating a marginal benefit. Thus, there is increased interest in applying targeted therapies for this disease. Areas covered: This review article summarizes the role of chemotherapeutic regimens for the treatment of BTC, and highlights key signal transduction pathways of interest for targeted inhibition...
March 17, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28292200/therapeutic-effects-of-methionine-sulfoximine-in-multiple-diseases-include-and-extend-beyond-inhibition-of-glutamine-synthetase
#17
William S A Brusilow, Tyler J Peters
Methionine sulfoximine (MSO), a well-characterized inhibitor of glutamine synthetase, displays significant therapeutic benefits in animal models for several human diseases. This amino acid might therefore be a viable candidate for drug development to treat diseases for which there are few effective therapies. Areas covered: We describe the effects of MSO on brain swelling occurring in overt hepatic encephalopathy resulting from liver failure, the effects of MSO on excitotoxic damage involved in amyotrophic lateral sclerosis (ALS) or resulting from stroke, and the effects of MSO on a model for an inflammatory immune response involved in a range of diseases...
March 15, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28127991/tshr-as-a-therapeutic-target-in-graves-disease
#18
Terry J Smith
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...
February 6, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28281906/pad4-pathophysiology-current-therapeutics-and-future-perspective-in-rheumatoid-arthritis
#19
Sindhu Koushik, Nivedita Joshi, Shruthi Nagaraju, Sameer Mahmood, Krishna Mudeenahally, Ramya Padmavathy, Sooriya Kumar Jegatheesan, Ramesh Mullangi, Sriram Rajagopal
Peptidyl arginine deiminase 4 (PAD4) is an enzyme that plays an important role in gene expression, turning out genetic code into functional products in the body. It is involved in a key post translational modification, which involves the conversion of arginine to citrulline. It regulates various processes such as apoptosis, innate immunity and pluripotency, while its dysregulation has a great impact on the genesis of various diseases. Over the last few years PAD4 has emerged as a potential therapeutic target for the treatment of rheumatoid arthritis (RA)...
April 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28281905/implications-of-toll-like-receptors-in-ebola-infection
#20
Amene Saghazadeh, Nima Rezaei
The potential roles of toll-like receptors (TLRs) in immunopathogenesis of Ebola virus disease should be unraveled to provoke possible prophylactic or therapeutic implications of TLRs for EVD. Areas covered: The Ebola virus (EBOV) infection virtually paralyses all the main mechanisms responsible for induction of type I interferon (IFN-I) response. To summarize, EBOV infection interferes with: a) the TIR-domain-containing adapter-inducing interferon-β (TRIF) pathway that is mediated by TLR3 and TLR4 signaling; b) the interferon regulatory factor 7 (IRF7) pathway that is stimulated by TLR7 and TLR9; c) the intracellular signaling that is induced by retinoic acid-inducible gene 1 (RIG-I)-like receptors (RLRs); and d) the autocrine/paracrine feedback loop that is mediated by the IFN-stimulated gene factor 3 (ISGF3) complex...
April 2017: Expert Opinion on Therapeutic Targets
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