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Current Opinion in Pharmacology

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https://www.readbyqxmd.com/read/28419894/muscle-cell-communication-in-development-and-repair
#1
REVIEW
Alexis R Demonbreun, Elizabeth M McNally
Under basal conditions, postnatal skeletal muscle displays little cell turnover. With injury, muscle initiates a rapid repair response to reseal damaged membrane, reactivating many developmental pathways to facilitate muscle regeneration and prevent tissue loss. Muscle precursor cells become activated accompanied by differentiation and fusion during both muscle growth and regeneration; inter-cellular communication is required for successful completion of these processes. Cellular communication is mediated by lipids, fusogenic membrane proteins, and exosomes...
April 15, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28407519/skeletal-muscle-autophagy-and-its-role-in-sarcopenia-and-organismal-aging
#2
REVIEW
Jianqin Jiao, Fabio Demontis
Sarcopenia, the loss of skeletal muscle mass and strength in the aged, is an important medical condition but its etiology is incompletely understood. Because autophagy promotes myofiber atrophy in the young, it was believed that autophagy inhibition would prevent sarcopenia. However, recent studies have revealed that autophagy actually maintains muscle mass and that its function declines during muscle aging. Consistently, boosting basal autophagy protects from age-related muscle dysfunction by promoting the selective degradation of misfolded proteins and dysfunctional organelles...
April 10, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28388508/mechanisms-of-cardioprotection-via-modulation-of-the-immune-response
#3
REVIEW
Gabriel A Grilo, Patti R Shaver, Lisandra E de Castro Brás
Both morbidity and mortality as a result of cardiovascular disease remain significant worldwide and account for approximately 31% of annual deaths in the US. Current research is focused on novel therapeutic strategies to protect the heart during and after ischemic events and from subsequent adverse myocardial remodeling. After cardiac insult, the immune system is activated and plays an essential role in the beginning, development, and resolution of the healing cascade. Uncontrolled inflammatory responses can cause chronic disease and exacerbate progression to heart failure and therefore, constitute a major area of focus of cardiac therapies...
April 4, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28388507/novel-protein-kinase-targets-in-vascular-smooth-muscle-therapeutics
#4
REVIEW
David A Tulis
Many signaling factors have been identified over the years that serve as mechanistic foundations for the pathogenesis and/or maintenance of cardiovascular disease (CVD). Of these, cyclic nucleotide-driven protein kinases in vascular smooth muscle (VSM) are of essential importance. Comprised primarily of cyclic AMP-dependent and cyclic GMP-dependent protein kinases, these ubiquitous signaling molecules have capacity to operate through numerous downstream effectors including vasodilator-stimulated phosphoprotein (VASP) to control aberrant VSM growth elemental to CVD...
April 4, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28340373/influence-of-sex-on-cardiovascular-drug-responses-role-of-estrogen
#5
REVIEW
Abdel A Abdel-Rahman
In this review we discuss the sex/estrogen-specific modulation of cardiovascular function and responses to current therapeutics. We discuss how anatomical differences such as a smaller kidney size, and lower glomerular filtration rate in females, reduce the clearance and increase the toxicity of some drugs in females. Other important sex differences include the dampening effect of estrogen on central sympathetic and renin angiotensin systems. Further, we discuss how a shift in myocardial redox status leads to paradoxical transformation of estrogen into a pro-inflammatory hormone...
March 21, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28288370/the-role-of-gpcrs-in-neurodegenerative-diseases-avenues-for-therapeutic-intervention
#6
REVIEW
Yunhong Huang, Nicholas Todd, Amantha Thathiah
Neurodegenerative diseases represent a large group of neurological disorders with heterogeneous clinical and pathological profiles. The majority of current therapeutic strategies provide temporary symptomatic relief but do not target the underlying disease pathobiology and thus do not affect disease progression. G protein-coupled receptors (GPCRs) are among the most successful targets for therapeutic development of central nervous system (CNS) disorders. Many current clinical therapeutic agents act by targeting this class of receptors and downstream signaling pathways...
March 10, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28135635/recent-advances-in-drug-discovery-of-gpcr-allosteric-modulators-for-neurodegenerative-disorders
#7
REVIEW
Robert Lütjens, Jean-Philippe Rocher
The activation or the inhibition of G-protein coupled receptors (GPCRs) implicated in the pathophysiology of neurodegenerative disorders is considered as a relevant approach for the treatment of these diseases. The modulation of the relevant GPCRs targets by positive or by negative allosteric modulators appears to be promising, the major challenge remaining the discovery of these molecules. In this review, we highlight the recent development in this field and the therapeutic potential of selected GPCRs allosteric modulators...
January 27, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28417881/understanding-gpcr-signaling-in-the-brain-the-path-to-cns-drug-discovery
#8
EDITORIAL
David Chatenet, Terence E Hébert
No abstract text is available yet for this article.
February 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27875804/optogenetic-approaches-for-dissecting-neuromodulation-and-gpcr-signaling-in-neural-circuits
#9
REVIEW
Skylar M Spangler, Michael R Bruchas
Optogenetics has revolutionized neuroscience by providing means to control cell signaling with spatiotemporal control in discrete cell types. In this review, we summarize four major classes of optical tools to manipulate neuromodulatory GPCR signaling: opsins (including engineered chimeric receptors); photoactivatable proteins; photopharmacology through caging-photoswitchable molecules; fluorescent protein based reporters and biosensors. Additionally, we highlight technologies to utilize these tools in vitro and in vivo, including Cre dependent viral vector expression and two-photon microscopy...
February 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27835800/contribution-of-heteromerization-to-g-protein-coupled-receptor-function
#10
REVIEW
Supriya A Gaitonde, Javier González-Maeso
G protein-coupled receptors (GPCRs) are a remarkably multifaceted family of transmembrane proteins that exert a variety of physiological effects. Although family A GPCRs are able to operate as monomers, there is increasing evidence that heteromerization represents a fundamental aspect of receptor function, trafficking and pharmacology. Most recently, it has been suggested that GPCR heteromers may play a crucial role as new molecular targets of heteromer-selective and bivalent ligands. The current review summarizes key recent developments in these topics...
February 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28027487/functional-selectivity-and-dualsteric-bitopic-gpcr-targeting
#11
REVIEW
Ramona Schrage, Evi Kostenis
Functional selectivity provides a new avenue to selectively engage particular pathways of the pleiotropic signaling repertoire of a G protein-coupled receptor. First examples for signaling biased compounds at the angiotensin II receptor and the μ opioid receptor have progressed to clinical trials and are promising in regard to selective activation of signaling pathways that can be linked to beneficial clinical outcomes. Dualsteric/bitopic hybrid compounds which consist of at least two pharmacophores combined in one single ligand are more recent examples for functionally selective ligands...
December 24, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27936408/biased-mu-opioid-receptor-ligands-a-promising-new-generation-of-pain-therapeutics
#12
REVIEW
Edward R Siuda, Richard Carr, David H Rominger, Jonathan D Violin
Opioid chemistry and biology occupy a pivotal place in the history of pharmacology and medicine. Morphine offers unmatched efficacy in alleviating acute pain, but is also associated with a host of adverse side effects. The advent of biased agonism at G protein-coupled receptors has expanded our understanding of intracellular signaling and highlighted the concept that certain ligands are able to differentially modulate downstream pathways. The ability to target one pathway over another has allowed for the development of biased ligands with robust clinical efficacy and fewer adverse events...
December 6, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27930943/analyzing-biased-responses-of-gpcr-ligands
#13
REVIEW
Besma Benredjem, Paul Dallaire, Graciela Pineyro
G protein-coupled receptors (GPCRs) are valuable targets for drug discovery. They exist in interconverting states differentially stabilized by diverse signaling partners. A ligand's capacity to distinguish among receptors associated with different partners is the basis of bias. This feature of GPCR signaling may allow development of ligands which specifically modulate effectors supporting desired actions. However, bias is time-dependent and cell-dependent such that in vitro bias may not predict bias displayed in vivo...
December 5, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27889687/role-of-inflammation-in-obesity-related-breast-cancer
#14
REVIEW
Elisa Crespi, Giulia Bottai, Libero Santarpia
Chronic inflammation associated with obesity is now recognized to be an important condition in promoting carcinogenesis and progression in breast cancer patients, mostly in postmenopausal women with tumors expressing estrogen and progesterone receptors. In obese patients, altered levels of several inflammatory mediators regulating aromatase and estrogen expression are one of the mechanisms responsible of increase breast cancer risk. Growing attention has also been paid to the local adipose inflammation and the role played by macrophages as determinants of breast cancer risk recurrence and prognosis...
December 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27886642/obesity-and-the-breast-cancer-methylome
#15
REVIEW
William B Coleman
Breast cancer is associated with risk factors such as advancing age and obesity. However, the linkages between these risk factors for breast cancer development and initiation of the disease are not yet clear. Obesity may drive breast cancer development through increases in circulating estrogens in postmenopausal women. Mammary cell susceptibility to neoplastic transformation requires both genetic and epigenetic alterations, including changes in DNA methylation. Obesity is also subject to epigenetic regulation...
December 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27883943/targeted-therapy-for-breast-cancer-and-molecular-mechanisms-of-resistance-to-treatment
#16
REVIEW
Guowei Gu, Derek Dustin, Suzanne Aw Fuqua
In recent years, clinical trials investigating new drugs and therapeutic combinations have led to promising advances in breast cancer therapy. Subtyping breast cancers into hormone receptor (HR) positive, epidermal growth factor receptor (HER2) positive, and triple negative breast cancer (TNBC) is currently the basis of diagnosing and treating this disease. In addition to endocrine and HER2-targeted therapies in their respective subtypes, evidence from recent preclinical studies have shown several targetable pathways that overcome resistance in the clinical setting...
December 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27876260/editorial-overview-endocrine-and-metabolic-diseases-adipocyte-dysfunction-fuels-signalings-for-breast-cancer-progression
#17
EDITORIAL
Sebastiano Andò
No abstract text is available yet for this article.
December 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27875786/inflammation-dysregulated-metabolism-and-aromatase-in-obesity-and-breast-cancer
#18
REVIEW
Heba Zahid, Evan R Simpson, Kristy A Brown
Obesity is associated with an increased risk of estrogen-dependent breast cancer after menopause. Adipose tissue undergoes important changes in obesity due to excess storage of lipids, leading to adipocyte cell death and the recruitment of macrophages. The resultant state of chronic low-grade inflammation is associated with the activation of NFkB signaling and elevated levels of aromatase, the rate-limiting enzyme in estrogen biosynthesis. This occurs not only in the visceral and subcutaneous fat, but also in the breast fat...
December 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27816025/leptin-obesity-and-breast-cancer-progress-to-understanding-the-molecular-connections
#19
REVIEW
Ines Barone, Cinzia Giordano, Daniela Bonofiglio, Sebastiano Andò, Stefania Catalano
Obesity has a complicated connection to both breast cancer risk and the clinical behaviour of the established disease. The obese setting provides a unique adipose tissue microenvironment that, in association with systemic endocrine modifications, promotes tumor initiation, primary growth, invasion, and metastatic progression. This review presents an overview of the clinical and experimental evidences highlighting the adipokine leptin as the most important molecular mediator of obesity-breast cancer axis. The research of leptin network operating in this context could launch a new field not only in the knowledge of risk factors for breast cancer but also in the development of leptin targeting drugs as promising anticancer agents...
December 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27750091/hedgehog-signaling-in-the-stomach
#20
REVIEW
Daniel Konstantinou, Nina Bertaux-Skeirik, Yana Zavros
The Hedgehog (Hh) signaling pathway not only plays a key part in controlling embryonic development, but in the adult stomach governs important cellular events such as epithelial cell differentiation, proliferation, gastric disease, and regeneration. In particular, Sonic Hedgehog (Shh) signaling has been well studied for its role in gastric physiology and pathophysiology. Shh is secreted from the gastric parietal cells and contributes to the regeneration of the epithelium in response to injury, or the development of gastritis during Helicobacter pylori infection...
December 2016: Current Opinion in Pharmacology
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