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Current Opinion in Pharmacology

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https://www.readbyqxmd.com/read/28528298/emerging-role-of-monoamine-oxidase-as-a-therapeutic-target-for-cardiovascular-disease
#1
REVIEW
Soni Deshwal, Moises Di Sante, Fabio Di Lisa, Nina Kaludercic
In the past decade, accumulating evidence highlighted the role of monoamine oxidases (MAOs) in cardiovascular disease (CVD). MAOs are flavoenzymes located in the outer mitochondrial membrane, responsible for the degradation of neurotransmitters and biogenic amines. During this process they generate hydrogen peroxide, aldehydes and ammonia, species that can target mitochondria and induce mitochondrial dysfunction and cardiomyocyte death. Indeed, MAO inhibition affords cardioprotection in several models of CVD, such as ischemia/reperfusion, heart failure and diabetes...
May 18, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28528297/biogenic-aldehydes-as-therapeutic-targets-for-cardiovascular-disease
#2
REVIEW
Margaret-Ann M Nelson, Shahid P Baba, Ethan J Andersonc
Aldehydes are continuously formed in biological systems through enzyme-dependent and spontaneous oxidation of lipids, glucose, and primary amines. These highly reactive, biogenic electrophiles can become toxic via covalent modification of proteins, lipids and DNA. Thus, agents that scavenge aldehydes through conjugation have therapeutic value for a number of major cardiovascular diseases. Several commonly-prescribed drugs (e.g., hydralazine) have been shown to have potent aldehyde-conjugating properties which may contribute to their beneficial effects...
May 18, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28527911/cancer-stem-cells-at-the-forefront-of-personalized-medicine-and-immunotherapy
#3
REVIEW
Micol E Fiori, Lidia Villanova, Ruggero De Maria
Cancer stem cells (CSCs) represent the main target of the current efforts to eradicate cancer, because of their ability to promote metastatic dissemination and survive cytotoxic therapies. Here, we highlight the potential of patient-derived CSCs as an in vitro and in vivo pre-clinical model and of liquid biopsy as a diagnostic, prognostic and predictive tool. We discuss recently developed therapeutic strategies aiming at specifically targeting the cancer stem cell population, particularly focusing on the latest advances in cancer immunotherapy...
May 18, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28527325/dyslipidemia-management-update
#4
REVIEW
Yingzi Chang, Jacques Robidoux
Association of hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD) is well established. Reducing low-density lipoprotein-cholesterol (LDL-C) and raising high-density lipoprotein-cholesterol (HDL-C) have been the therapeutic targets to reduce the risk of ASCVD. Cholesterol-lowering medications have been used to provide both primary and secondary prevention of ASCVD for many years by reducing the absorption and reabsorption, promoting excretion, or decreasing the synthesis of cholesterol. Within the past five years, several new classes of cholesterol-lowering drugs have been tested and approved for patients with hypercholesterolemia that are not well controlled by conventional therapy (ezetimibe, bile-acid sequestrants, and statins)...
May 17, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28525818/hypertension-update-jnc8-and-beyond
#5
REVIEW
Tara Shrout, David W Rudy, Michael T Piascik
Hypertension is the most preventable major risk factor for cardiovascular morbidity and mortality. The etiology of elevated blood pressure is a complex process involving the interaction of genetics, demographics, comorbid disorders, and environmental influences. Effective hypertensive therapy has been shown to reduce cardiovascular morbidity and mortality. JNC reports have served as a valuable source of guidelines, and JNC 8 is the most recently updated guideline for the prevention, diagnosis, and treatment of hypertension...
May 16, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28486179/pharmacological-advances-for-treatment-in-duchenne-muscular-dystrophy
#6
REVIEW
Simon Guiraud, Kay E Davies
Duchenne muscular dystrophy (DMD) is a lethal, X-linked muscle-wasting disease caused by lack of dystrophin, essential for muscle fibre integrity. Despite extensive pre-clinical studies, development of an effective treatment has proved challenging. More recently, significant progress has been made with the first drug approval using a genetic approach and the application of pharmacological agents which slow the progression of the disease. Drug development for DMD has mainly used two strategies: (1) the restoration of dystrophin expression or the expression of the compensatory utrophin protein as an efficient surrogate, and (2) the mitigation of secondary downstream pathological mechanisms...
May 6, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28482281/ace-and-sglt2-inhibitors-the-future-for-non-diabetic-and-diabetic-proteinuric-renal-disease
#7
REVIEW
Norberto Perico, Piero Ruggenenti, Giuseppe Remuzzi
Most chronic nephropathies progress relentlessly to end-stage kidney disease. Research in animals and humans has helped our understanding of the mechanisms of chronic kidney disease progression. Current therapeutic strategies to prevent or revert renal disease progression focus on reduction of urinary protein excretion and blood pressure control. Blockade of the renin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitors and/or angiotensin II type 1 receptor blockers is the most effective treatment to achieve these purposes in non-diabetic and diabetic proteinuric renal diseases...
May 5, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28472742/cell-cell-communication-in-bone-development-and-whole-body-homeostasis-and-pharmacological-avenues-for-bone-disorders
#8
REVIEW
Young-Eun Park, David S Musson, Dorit Naot, Jillian Cornish
Cell-cell communication plays a crucial role in bone development and maintenance, in health and disease. Our knowledge of the signalling pathways that regulate the communication of osteoblasts, osteoclasts and osteocytes is improving with time, giving us a better understanding of the regulation of the bone remodelling process. Bone cell communication has wider significance than the local tissue environment, however, with bone derived factors playing a role in whole-body homeostasis, including energy metabolism and kidney function...
May 1, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28456094/new-biologics-in-the-treatment-of-rare-glomerular-diseases-of-childhood
#9
REVIEW
Paolo Cravedi, Andrea Angeletti, Giuseppe Remuzzi
Minimal change disease and focal segmental glomerulosclerosis are rare but important causes of end-stage kidney disease in children. Though their pathogenesis is still unclear, evidence of immune abnormalities provided the background for the use of immunosuppressive drugs, such as corticosteroids, calcineurin inhibitors, antiproliferative and alkylating agents. Unfortunately, these treatments fail to achieve a sustained remission in a significant portion of patients and are burdened by significant toxicities...
April 26, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28441626/myobolites-muscle-derived-metabolites-with-paracrine-and-systemic-effects
#10
REVIEW
Ayon Ibrahim, Michael Neinast, Zoltan P Arany
Intracellular metabolism in skeletal muscle has been studied for more than a century and is the stuff of textbooks. In contrast, the extracellular secretion of metabolites by muscle cells, and their effects on non-muscle cells near or far, has been investigated much less extensively. Here, we describe a number of cases in which striated muscle secretes a metabolite that elicits complex responses in other cells or tissues, with involvements in normal physiology as well as obesity, type II diabetes, and cardiac remodeling...
April 22, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28437711/cardiomyocyte-ca-2-homeostasis-as-a-therapeutic-target-in-heart-failure-with-reduced-and-preserved-ejection-fraction
#11
REVIEW
Deborah Peana, Timothy L Domeier
Heart failure is a highly prevalent syndrome of multiple etiologies and associated comorbidities, and aberrant intracellular Ca(2+) homeostasis is a hallmark finding in heart failure patients. The cyclical changes in Ca(2+) concentration within cardiomyocytes control cycles of cardiac contraction and relaxation, and dysregulation of Ca(2+) handling processes leads to systolic dysfunction, diastolic dysfunction, and adverse remodeling. For this reason, greater understanding of Ca(2+) handling mechanisms in heart failure is critical for selection of appropriate treatment strategies...
April 22, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28419894/muscle-cell-communication-in-development-and-repair
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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/28417881/understanding-gpcr-signaling-in-the-brain-the-path-to-cns-drug-discovery
#18
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/28135635/recent-advances-in-drug-discovery-of-gpcr-allosteric-modulators-for-neurodegenerative-disorders
#19
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...
February 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27936408/biased-mu-opioid-receptor-ligands-a-promising-new-generation-of-pain-therapeutics
#20
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...
February 2017: Current Opinion in Pharmacology
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