The role of DNA methylation in epigenetics of aging
Publication date: Available online 9 November 2018Source: Pharmacology & TherapeuticsAuthor(s): Archana Unnikrishnan, Willard M. Freeman, Jordan Jackson, Jonathan D. Wren, Hunter Porter, Arlan RichardsonAbstractRecent research suggests that epigenetics, especially DNA methylation, plays a mechanistic role in aging. Epigenetic clocks, which measure changes in a few hundred specific CpG sites, can accurately predict chronological age in a variety of species, including humans. These clocks are currently the best biomarkers for predicting mortality in humans. Additionally, several studies have characterized the effects of ...
Source: Pharmacology and Therapeutics - November 11, 2018 Category: Drugs & Pharmacology Source Type: research

The sphingosine kinase-1/sphingosine-1-phosphate axis in cancer: Potential target for anticancer therapy
Publication date: Available online 19 October 2018Source: Pharmacology & TherapeuticsAuthor(s): Xiangjin Zheng, Wan Li, Liwen Ren, Jinyi Liu, Xiaocong Pang, Xiuping Chen, De Kang, Jinhua Wang, Guanhua DuAbstractSphingolipid metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate (S1P), play many important roles in cellular activities. Ceramide and sphingosine inhibit cell proliferation and induce cell apoptosis while S1P has the opposite effect. Maintaining a metabolic balance of sphingolipids is essential for growth and development of cells. Sphingosine kinase (SPHK) is an important regulator for keepin...
Source: Pharmacology and Therapeutics - October 30, 2018 Category: Drugs & Pharmacology Source Type: research

The neuropsychopharmacology of cannabis: a review of human imaging studies
We describe the effects of drug exposure during development, implications for understanding psychosis and cannabis use disorder, and methodological considerations. Greater understanding of the precise mechanisms underlying the effects of cannabis may also give rise to new treatment targets. (Source: Pharmacology and Therapeutics)
Source: Pharmacology and Therapeutics - October 20, 2018 Category: Drugs & Pharmacology Source Type: research

Organic Anion Transporting Polypeptide (OATP) transporter expression, localization and function in the human intestine
Publication date: Available online 19 October 2018Source: Pharmacology & TherapeuticsAuthor(s): Stefan OswaldAbstractIntestinal transporter proteins, along with drug metabolizing enzymes, play a major role in the disposition of orally administered drugs, nutrients and xenobiotics. In this regard, efflux transporters such as ABCB1 and ABCG2 can limit oral bioavailability, while uptake carriers such as PEPT1 have the potential to facilitate intestinal absorption. In contrast to the extensive information on intestinal efflux pumps, detailed knowledge about the respective uptake carriers is rather limited. During the last ...
Source: Pharmacology and Therapeutics - October 20, 2018 Category: Drugs & Pharmacology Source Type: research

The Sphingosine Kinase-1 / Sphingosine-1-Phosphate Axis in Cancer: Potential Target for Anticancer Therapy
Publication date: Available online 19 October 2018Source: Pharmacology & TherapeuticsAuthor(s): Xiangjin Zheng, Wan Li, Liwen Ren, Jinyi Liu, Xiaocong Pang, Xiuping Chen, De Kang, Jinhua Wang, Guanhua DuAbstractSphingolipid metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate (S1P), play many important roles in cellular activities. Ceramide and sphingosine inhibit cell proliferation and induce cell apoptosis while S1P has the opposite effect. Maintaining a metabolic balance of sphingolipids is essential for growth and development of cells. Sphingosine kinase (SPHK) is an important regulator for keepin...
Source: Pharmacology and Therapeutics - October 20, 2018 Category: Drugs & Pharmacology Source Type: research

P53 in kidney injury and repair: Mechanism and therapeutic potentials
Publication date: Available online 19 October 2018Source: Pharmacology & TherapeuticsAuthor(s): Chengyuan Tang, Zhengwei Ma, Jiefu Zhu, Zhiwen Liu, Yuxue Liu, Yu Liu, Juan Cai, Zheng DongAbstractAcute kidney injury (AKI) is a major kidney disease with poor clinical outcome. Besides its acute consequence of high mortality, AKI may also contribute significantly to the occurrence and progression of chronic kidney diseases (CKD). Accumulating evidence has demonstrated that maladaptive and incomplete kidney repair after AKI leads to the development of renal fibrosis and, ultimately, CKD. p53, a well-known tumor suppressor, ...
Source: Pharmacology and Therapeutics - October 20, 2018 Category: Drugs & Pharmacology Source Type: research

Revisiting the role of dihydroorotate dehydrogenase as a therapeutic target for cancer
Publication date: Available online 19 October 2018Source: Pharmacology & TherapeuticsAuthor(s): Joseph T. Madak, Armand Bankhead, Christine R. Cuthbertson, Hollis D. Showalter, Nouri NeamatiAbstractIdentified as a hallmark of cancer, metabolic reprogramming allows cancer cells to rapidly proliferate, resist chemotherapies, invade, metastasize, and survive a nutrient-deprived microenvironment. Rapidly growing cells depend on sufficient concentrations of nucleotides to sustain proliferation. One enzyme essential for the de novo biosynthesis of pyrimidine-based nucleotides is dihydroorotate dehydrogenase (DHODH), a known ...
Source: Pharmacology and Therapeutics - October 20, 2018 Category: Drugs & Pharmacology Source Type: research

Role of the 12-Lipoxygenase Pathway in Diabetes Pathogenesis and Complications
Publication date: Available online 19 October 2018Source: Pharmacology & TherapeuticsAuthor(s): A.D. Dobrian, M.A. Morris, D.A. Taylor-Fishwick, T.R. Holman, Y. Imai, R.G. Mirmira, J.L. NadlerAbstract12-lipoxygenase (12-LOX) is one of several enzyme isoforms responsible for the metabolism of arachidonic acid and other poly-unsaturated fatty acids to both pro- and anti-inflammatory lipid mediators. Mounting evidence has shown that 12-LOX plays a critical role in the modulation of inflammation at multiple checkpoints during diabetes development. Due to this, interventions to limit pro-inflammatory 12-LOX metabolites eith...
Source: Pharmacology and Therapeutics - October 20, 2018 Category: Drugs & Pharmacology Source Type: research

Antifungal drugs: New insights in research & development
Publication date: Available online 19 October 2018Source: Pharmacology & TherapeuticsAuthor(s): André Moraes Nicola, Patrícia Albuquerque, Hugo Costa Paes, Larissa Fernandes, Fabricio F. Costa, Erika Seki Kioshima, Ana Karina Rodrigues Abadio, Anamélia Lorenzetti Bocca, Maria Sueli FelipeAbstractThe need for better antifungal therapy is commonly accepted in view of the high mortality rates associated with systemic infections, the low number of available antifungal classes, their associated toxicity and the increasing number of infections caused by strains with natural or acquired resistance. The ur...
Source: Pharmacology and Therapeutics - October 20, 2018 Category: Drugs & Pharmacology Source Type: research

Targeting Mcl-1 and Other Bcl-2 Family Member Proteins in Cancer Therapy
Publication date: Available online 19 October 2018Source: Pharmacology & TherapeuticsAuthor(s): Ryuji Yamaguchi, Lydia Lartigue, Guy PerkinsAbstractRegulation of both the extrinsic and the mitochondria-dependent intrinsic apoptotic pathways plays a key role in the development of the hematopoietic system, for sustaining cell survival during generation of various cell types, in eliminating cells with dual identities such as CD4/CD8 double-positive cells1,2, for sustaining cells during the rapid clonal expansion phase3, as well as eliminating cells during the contraction phase4. The anti-apoptotic protein Mcl-1 is necessa...
Source: Pharmacology and Therapeutics - October 20, 2018 Category: Drugs & Pharmacology Source Type: research

Editorial Board
Publication date: November 2018Source: Pharmacology & Therapeutics, Volume 191Author(s): (Source: Pharmacology and Therapeutics)
Source: Pharmacology and Therapeutics - October 16, 2018 Category: Drugs & Pharmacology Source Type: research

Statins: adverse reactions, oxidative stress and metabolic interactions
Publication date: Available online 12 October 2018Source: Pharmacology & TherapeuticsAuthor(s): Aimei Liu, Qinghua Wu, Jingchao Guo, Irma Ares, José-Luis Rodríguez, María-Rosa Martínez-Larrañaga, Zonghui Yuan, Arturo Anadón, Xu Wang, María-Aránzazu MartínezABSTRACTStatins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are currently the most effective lipid-lowering drugs, effectively reducing the plasma total cholesterol and low-density lipoprotein, while also decreasing three triacylglycerols and increasing plasma high-density lipoprotein to ...
Source: Pharmacology and Therapeutics - October 14, 2018 Category: Drugs & Pharmacology Source Type: research

Non-vitamin K oral anticoagulants (NOAC) and the risk of myocardial infarction: Differences between factor IIa and factor Xa inhibition?
Publication date: Available online 12 October 2018Source: Pharmacology & TherapeuticsAuthor(s): Amin Polzin, Lisa Dannenberg, Georg Wolff, Carolin Helten, Alina Achillles, Thomas Hohlfeld, Tobias Zeus, Malte Kelm, Steffen Massberg, Tobias PetzoldAbstractGuidelines already recommend non-vitamin K oral anticoagulants (NOAC) over vitamin-K antagonists (VKA) for stroke prevention in patients with atrial fibrillation. However, recommendations are lacking with respect to which NOAC to use. At the moment, NOACs may employ two different molecular mechanisms: Factor IIa inhibition (dabigatran) and factor Xa inhibition (apixaban...
Source: Pharmacology and Therapeutics - October 12, 2018 Category: Drugs & Pharmacology Source Type: research

Myocardial metabolism in heart failure: Purinergic signalling and other metabolic concepts
Publication date: Available online 25 August 2018Source: Pharmacology & TherapeuticsAuthor(s): Andreas L. Birkenfeld, Jens Jordan, Markus Dworak, Tobias Merkel, Geoffrey BurnstockAbstractDespite significant therapeutic advances in heart failure (HF) therapy, the morbidity and mortality associated with this disease remains unacceptably high. The concept of metabolic dysfunction as an important underlying mechanism in HF is well established.Cardiac function is inextricably linked to metabolism, with dysregulation of cardiac metabolism pathways implicated in a range of cardiac complications, including HF. Modulation of ca...
Source: Pharmacology and Therapeutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Neutrophils in tPA-induced hemorrhagic transformations: Main culprit, accomplice or innocent bystander?
Publication date: Available online 18 September 2018Source: Pharmacology & TherapeuticsAuthor(s): Thavarak Ouk, Camille Potey, Ilaria Maestrini, Maud Petrault, Anne-Marie Mendyk, Didier Leys, Regis Bordet, Sophie GautierAbstractThe risk of intracerebral hemorrhage still greatly limits the use of tPA in stroke patients. Research is ongoing in order to identify the pathophysiological mechanisms at play, detect predictive biomarkers and discover new pharmacological targets to develop preventive or curative treatments. Going through experimental and clinical studies, this review focuses on the role of neutrophils as key pr...
Source: Pharmacology and Therapeutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

DYRK1A and cognition: A lifelong relationship
Publication date: Available online 28 September 2018Source: Pharmacology & TherapeuticsAuthor(s): Maria L. Arbones, Aurore Thomazeau, Akiko Nakano-Kobayashi, Masatoshi Hagiwara, Jean M. DelabarAbstractThe dosage of the serine threonine kinase DYRK1A is critical in the central nervous system (CNS) during development and aging. This review analyzes the functions of this kinase by considering its interacting partners and pathways. The role of DYRK1A in controlling the differentiation of prenatal newly formed neurons is presented separately from its role at the pre- and post-synaptic levels in the adult CNS; its effects on...
Source: Pharmacology and Therapeutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Targeting Programmed Cell Death -1 (PD-1) and Ligand (PD-L1): A new era in cancer active immunotherapy
This article provides a comprehensive review of the early and late phase trials that led to the regulatory approval of all five PD1- PDL-1 inhibitors in the corresponding cancer types. It presents available data on the combinations of PD1- PDL-1 inhibitors with other therapies (immunotherapy, targeted therapy and chemotherapy), the toxicity profile of the PD1- PDL-1 inhibitors and ongoing trials testing the efficacy of these agents in cancer types beyond those that have been addressed already. Finally, current and future challenges in the application of PD-1 and PD-L1 inhibitors are discussed with emphasis on the role of p...
Source: Pharmacology and Therapeutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Hybrid epithelial/mesenchymal phenotypes promote metastasis and therapy resistance across carcinomas
Publication date: Available online 28 September 2018Source: Pharmacology & TherapeuticsAuthor(s): Mohit Kumar Jolly, Jason A. Somarelli, Maya Sheth, Adrian Biddle, Satyendra C. Tripathi, Andrew J. Armstrong, Samir M. Hanash, Sharmila A. Bapat, Annapoorni Rangarajan, Herbert LevineAbstractCancer metastasis and therapy resistance are the major unsolved clinical challenges, and account for nearly all cancer-related deaths. Both metastasis and therapy resistance are fueled by epithelial plasticity, the reversible phenotypic transitions between epithelial and mesenchymal phenotypes, including epithelial-mesenchymal transiti...
Source: Pharmacology and Therapeutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

The role of flavonoids in autoimmune diseases: Therapeutic updates
Publication date: Available online 28 September 2018Source: Pharmacology & TherapeuticsAuthor(s): Kannan R.R. Rengasamy, Haroon Khan, Shanmugaraj Gowrishankar, Ricardo J.L. Lagoa, Fawzi M. Mahomoodally, Ziyad Khan, Shanoo Suroowan, Devesh Tewari, Gokhan Zengin, Sherif T.S. Hassan, Shunmugiah Karutha PandianAbstractFlavonoids are natural polyphenolic compounds which are included in a panoply of drugs and used to treat and/or manage human ailments such as metabolic, cardiovascular, neurological disorders and cancer. Thus, the purpose of this review is to emphasize the importance of flavonoids for the treatment of autoimm...
Source: Pharmacology and Therapeutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Corrigendum to “Readers of DNA methylation, the MBD family as potential therapeutic targets” [Pharmacology & Therapeutics 184 (1) (2018) 98-111]
Publication date: October 2018Source: Pharmacology & Therapeutics, Volume 190Author(s): Gordon D. Ginder, David C. Williams (Source: Pharmacology and Therapeutics)
Source: Pharmacology and Therapeutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Editorial Board
Publication date: October 2018Source: Pharmacology & Therapeutics, Volume 190Author(s): (Source: Pharmacology and Therapeutics)
Source: Pharmacology and Therapeutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Acetylcholine signaling system in progression of lung cancers
Publication date: Available online 3 October 2018Source: Pharmacology & TherapeuticsAuthor(s): Jamie R. Friedman, Stephen D. Richbart, Justin C. Merritt, Kathleen C. Brown, Nicholas A. Nolan, Austin T. Akers, Jamie K. Lau, Zachary R. Robateau, Sarah L. Miles, Piyali DasguptaAbstractThe neurotransmitter acetylcholine (ACh) acts as an autocrine growth factor for human lung cancer. Several lines of evidence show that lung cancer cells express all of the proteins required for the uptake of choline (choline transporter 1, choline transporter-like proteins) synthesis of ACh (choline acetyltransferase, carnitine acetyltransfe...
Source: Pharmacology and Therapeutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Fighting against depression with TREK-1 blockers: Past and future. A focus on spadin
Publication date: Available online 3 October 2018Source: Pharmacology & TherapeuticsAuthor(s): Alaeddine Djillani, Mariel Pietri, Jean Mazella, Catherine Heurteaux, Marc BorsottoAbstractDepression is a devastating mood disorder and a leading cause of disability worldwide. Depression affects approximately one in five individuals in the world and represents heavy economic and social burdens. The neurobiological mechanisms of depression are not fully understood, but evidence highlights the role of monoamine neurotransmitter balance. Several antidepressants (ADs) are marketed to treat depression and related mood disorders....
Source: Pharmacology and Therapeutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Endothelins in inflammatory neurological diseases
Publication date: Available online 3 October 2018Source: Pharmacology & TherapeuticsAuthor(s): Pedro D'Orleans-Juste, Oscar Bate Akide Ndunge, Louisane Desbiens, Herbert B. Tanowitz, Mahalia S. DesruisseauxAbstractEndothelins were discovered more than thirty years ago as potent vasoactive compounds. Beyond their well-documented vasomodulatory properties, however, the contributions of the endothelin pathway have been demonstrated in several neuroinflammatory processes and the peptides have been reported as a clinically relevant biomarkers in neurodegenerative diseases. Several published works suggest that endothelin-1 g...
Source: Pharmacology and Therapeutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Roles of DNA repair enzyme OGG1 in innate immunity and its significance for lung cancer
Publication date: Available online 19 September 2018Source: Pharmacology & TherapeuticsAuthor(s): Spiros Vlahopoulos, Maria Adamaki, Nikolas Khoury, Vassilis Zoumpourlis, Istvan BoldoghAbstractCytokines are pivotal mediators of the immune response, and their coordinated expression protects host tissue from excessive damage and oxidant stress. Nevertheless, the development of lung pathology, including asthma, chronic obstructive pulmonary disease, and ozone-induced lung injury, is associated with oxidant stress; as evidence, there is a significant increase in levels of the modified guanine base 7,8-dihydro-8-oxoguanine ...
Source: Pharmacology and Therapeutics - September 20, 2018 Category: Drugs & Pharmacology Source Type: research

Roles of DNA repair enzyme OGG1 in innate immunity and its significance for lung cancer
Publication date: Available online 18 September 2018Source: Pharmacology & TherapeuticsAuthor(s): Spiros Vlahopoulos, Maria Adamaki, Nikolas Khoury, Vassilis Zoumpourlis, Istvan BoldoghAbstractCytokines are pivotal mediators of the immune response, and their coordinated expression protects host tissue from excessive damage and oxidant stress. Nevertheless, the development of lung pathology, including asthma, chronic obstructive pulmonary disease, and ozone-induced lung injury, is associated with oxidant stress; as evidence, there is a significant increase in levels of the modified guanine base 7,8-dihydro-8-oxoguanine ...
Source: Pharmacology and Therapeutics - September 19, 2018 Category: Drugs & Pharmacology Source Type: research

TSPO in diverse CNS pathologies and psychiatric disease: A critical review and a way forward
Publication date: Available online 4 September 2018Source: Pharmacology & TherapeuticsAuthor(s): Tomás R. GuilarteAbstractThe use of Translocator Protein 18 kDa (TSPO) as a clinical neuroimaging biomarker of brain injury and neuroinflammation has increased exponentially in the last decade. There has been a furious pace in the development of new radiotracers for TSPO positron emission tomography (PET) imaging and its use has now been extensively described in many neurological and mental disorders. This fast pace of research and the ever-increasing number of new laboratories entering the field often times lack a...
Source: Pharmacology and Therapeutics - September 6, 2018 Category: Drugs & Pharmacology Source Type: research

Druggable Targets in the Rho pathway and their promise for therapeutic control of blood pressure
Publication date: Available online 4 September 2018Source: Pharmacology & TherapeuticsAuthor(s): Rachel A. Dee, Kevin D. Mangum, Xue Bai, Christopher P. Mack, Joan M. TaylorAbstractThe prevalence of high blood pressure (also known as hypertension) has steadily increased over the last few decades. Known as a silent killer, hypertension increases the risk for cardiovascular disease and can lead to stroke, heart attack, kidney failure and associated sequela. While numerous hypertensive therapies are currently available, it is estimated that only half of medicated patients exhibit blood pressure control. This signifies the...
Source: Pharmacology and Therapeutics - September 6, 2018 Category: Drugs & Pharmacology Source Type: research

Genetic variants in major depressive disorder: From pathophysiology to therapy
Publication date: Available online 4 September 2018Source: Pharmacology & TherapeuticsAuthor(s): Xenia Gonda, Peter Petschner, Nora Eszlari, Daniel Baksa, Andrea Edes, Peter Antal, Gabriella Juhasz, Gyorgy BagdyAbstractIn spite of promising preclinical results there is a decreasing number of new registered medications in major depression. The main reason behind this fact is the lack of confirmation in clinical studies for the assumed, and in animals confirmed, therapeutic results. This suggests low predictive value of animal studies for central nervous system disorders. One solution for identifying new possible targets...
Source: Pharmacology and Therapeutics - September 6, 2018 Category: Drugs & Pharmacology Source Type: research

Zinc signaling and epilepsy
Publication date: Available online 24 August 2018Source: Pharmacology & TherapeuticsAuthor(s): Urszula Doboszewska, Katarzyna Młyniec, Aleksandra Wlaź, Ewa Poleszak, Gabriel Nowak, Piotr WlaźAbstractEvidence from both preclinical and clinical studies suggest the importance of zinc homeostasis in seizures/epilepsy. Undoubtedly, zinc, via modulation of a variety of targets, is necessary for maintaining the balance between neuronal excitation and inhibition, while an imbalance between excitation and inhibition underlies seizures. However, the relationship between zinc signaling and seizures/epilepsy is complex as both ...
Source: Pharmacology and Therapeutics - August 25, 2018 Category: Drugs & Pharmacology Source Type: research

Harnessing CXCL12 signaling to protect and preserve functional β-cell mass and for cell replacement in type 1 diabetes
Publication date: Available online 24 August 2018Source: Pharmacology & TherapeuticsAuthor(s): David A. Alagpulinsa, Jenny J.L. Cao, Don Sobell, Mark C. PoznanskyAbstractType 1 diabetes (T1D) is a complex multifactorial disease characterized by autoimmune destruction of insulin-producing pancreatic β cells. Our understanding of the pathogenic mechanisms and natural history of T1D has evolved significantly over the past two decades; we can efficiently predict high-risk individuals, early diagnose the disease and stage progression. Fortuitously, novel in vitro differentiation protocols for generating functional &bet...
Source: Pharmacology and Therapeutics - August 25, 2018 Category: Drugs & Pharmacology Source Type: research

Myocardial metbolism in heart failure: Purinergic signalling and other metabolic concepts
Publication date: Available online 25 August 2018Source: Pharmacology & TherapeuticsAuthor(s): Andreas L. Birkenfeld, Jens Jordan, Markus Dworak, Tobias Merkel, Geoffrey BurnstockAbstractDespite significant therapeutic advances in heart failure (HF) therapy, the morbidity and mortality associated with this disease remains unacceptably high. The concept of metabolic dysfunction as an important underlying mechanism in HF is well established.Cardiac function is inextricably linked to metabolism, with dysregulation of cardiac metabolism pathways implicated in a range of cardiac complications, including HF. Modulation of ca...
Source: Pharmacology and Therapeutics - August 25, 2018 Category: Drugs & Pharmacology Source Type: research

Extracellular Matrix Roles in Cardiorenal Fibrosis: Potential Therapeutic Targets for CVD and CKD in the Elderly
Publication date: Available online 25 August 2018Source: Pharmacology & TherapeuticsAuthor(s): Hiroe Toba, Merry L. LindseyAbstractWhereas hypertension, diabetes, and dyslipidemia are age-related risk factors for cardiovascular disease (CVD) and chronic kidney disease (CKD), aging alone is an independent risk factor. With advancing age, the heart and kidney gradually but significantly undergo inflammation and subsequent fibrosis, which eventually results in an irreversible decline in organ physiology. Through cardiorenal network interactions, cardiac dysfunction leads to and responds to renal injury, and both facilitat...
Source: Pharmacology and Therapeutics - August 25, 2018 Category: Drugs & Pharmacology Source Type: research

Neurobiology and Therapeutic Applications of Neurotoxins Targeting Transmitter Release
Publication date: Available online 25 August 2018Source: Pharmacology & TherapeuticsAuthor(s): Saak V. Ovsepian, Valerie B. O’Leary, Naira M. Ayvazyan, Ahmed Al-Sabi, Vasilis Ntziachristos, J. Oliver DollyABSTRACTSynaptic transmission is a fundamental neurobiological process enabling exchange of signals between neurons as well as neurons and their non-neuronal effectors. The complex molecular machinery of the synaptic vesicle cycle and transmitter release has emerged and developed in the course of the evolutionary race, to ensure adaptive gain and survival of the fittest. In parallel, a generous arsenal of biomol...
Source: Pharmacology and Therapeutics - August 25, 2018 Category: Drugs & Pharmacology Source Type: research

Depression and schizophrenia viewed from the perspective of amino acidergic neurotransmission: Antipodes of psychiatric disorders
Publication date: Available online 25 August 2018Source: Pharmacology & TherapeuticsAuthor(s): Joanna M. Wierońska, Andrzej PilcAbstractDepression and schizophrenia are burdensome, costly serious and disabling mental disorders. Moreover the existing treatments are not satisfactory. As amino-acidergic (AA) neurotransmitters built a vast majority of brain neurons, in this article we plan to focus on drugs influencing AA neurotransmission in both diseases: we will discuss several facts concerning glutamatergic and GABA-ergic neurotransmission in these diseases, based mainly on preclinical experiments that used stimulator...
Source: Pharmacology and Therapeutics - August 25, 2018 Category: Drugs & Pharmacology Source Type: research

Interactions between dyslipidemia and the immune system and their relevance as putative therapeutic targets in atherosclerosis
Publication date: Available online 25 August 2018Source: Pharmacology & TherapeuticsAuthor(s): Michael Lacy, Dorothee Atzler, Rongqi Liu, Menno de Winther, Christian Weber, Esther LutgensAbstractCardiovascular disease (CVD) continues to be a leading cause of death worldwide with atherosclerosis being the major underlying pathology. The interplay between lipids and immune cells is believed to be a driving force in the chronic inflammation of the arterial wall during atherogenesis. Atherosclerosis is initiated as lipid particles accumulate and become trapped in vessel walls. The subsequent immune response, involving both...
Source: Pharmacology and Therapeutics - August 25, 2018 Category: Drugs & Pharmacology Source Type: research

Air pollution and resistance to inhaled glucocorticoids: Evidence, mechanisms and gaps to fill
We describe mechanisms that may contribute to reductions in glucocorticoid responsiveness following air pollution exposure, including changes to phosphorylation or oxidation of the glucocorticoid receptor, repression by cytokines, or inflammatory pathways, and epigenetic effects. Possible interactions between air pollution and respiratory infections are also briefly discussed. Finally, we detail a number of therapies that may boost glucocorticoid effectiveness or reverse resistance in the presence of air pollution, and comment on the beneficial effects of engineering controls, such as air filtration and asthma action plans...
Source: Pharmacology and Therapeutics - August 21, 2018 Category: Drugs & Pharmacology Source Type: research

Epigenome modifiers and metabolic rewiring: new frontiers in therapeutics
Publication date: Available online 17 August 2018Source: Pharmacology & TherapeuticsAuthor(s): Alessandra Ferrari, Raffaella Longo, Rui Silva, Nico Mitro, Donatella Caruso, Emma De Fabiani, Maurizio CrestaniAbstractIn the last decade numerous publications highlighted the connection between metabolism and epigenetics in different physiological and pathological conditions. The availability of metabolites for cells represents indeed a crucial factor, which is able to condition cell fate and development, differentiation and proliferation partially trough epigenetic control. This tight link provides novel therapeutic possib...
Source: Pharmacology and Therapeutics - August 17, 2018 Category: Drugs & Pharmacology Source Type: research

Senescence and senotherapeutics: a new field in cancer therapy
Publication date: Available online 16 August 2018Source: Pharmacology & TherapeuticsAuthor(s): Vassilios Myrianthopoulos, Konstantinos Evangelou, Panagiotis V.S. Vasileiou, Tomer Cooks, Theodoros P. Vassilakopoulos, Gerassimos A. Pangalis, Myrsini Kouloukoussa, Christos Kittas, Alexandros G. Georgakilas, Vassilis G. GorgoulisAbstractCellular senescence is a stress response mechanism ensuring homeostasis. Its temporal activation during embryonic development or normal adult life is linked with beneficial properties. In contrast, persistent (chronic) senescence seems to exert detrimental effects fostering aging and age-re...
Source: Pharmacology and Therapeutics - August 16, 2018 Category: Drugs & Pharmacology Source Type: research

Targeting oncogenic drivers in lung cancer: Recent progress, current challenges and future opportunities
Publication date: Available online 16 August 2018Source: Pharmacology & TherapeuticsAuthor(s): Satoshi Yoda, Ibiayi Dagogo-Jack, Aaron N. HataAbstractTargeted therapies have changed the landscape of treatments for non-small cell lung cancer (NSCLC). Specific targeted therapies have been approved for NSCLC patients harboring genetic alterations in four oncogenes, and agents targeting additional oncogenic drivers are under investigation. Standard first-line chemotherapy has been supplanted by these targeted therapies due to superior efficacy and lower toxicity. Despite excellent response rates and durable responses in so...
Source: Pharmacology and Therapeutics - August 16, 2018 Category: Drugs & Pharmacology Source Type: research

Editorial Board
Publication date: September 2018Source: Pharmacology & Therapeutics, Volume 189Author(s): (Source: Pharmacology and Therapeutics)
Source: Pharmacology and Therapeutics - August 13, 2018 Category: Drugs & Pharmacology Source Type: research

Anti-platelet drugs and their necessary interaction with endothelial mediators and platelet cyclic nucleotides for therapeutic efficacy
Publication date: Available online 4 August 2018Source: Pharmacology & TherapeuticsAuthor(s): Rebecca B. Knowles, Timothy D. WarnerAbstractFor many millions of patients at secondary risk of coronary thrombosis pharmaceutical protection is supplied by dual anti-platelet therapy. Despite substantial therapeutic developments over the last decade recurrent thrombotic events occur, highlighting the need for further optimisation of therapies. Importantly, but often ignored, anti-platelet drugs interact with cyclic nucleotide systems in platelets and these are the same systems that mediate key endogenous pathways of platelet ...
Source: Pharmacology and Therapeutics - August 4, 2018 Category: Drugs & Pharmacology Source Type: research

Targeting TLRs and the Inflammasome in systemic sclerosis
Publication date: Available online 4 August 2018Source: Pharmacology & TherapeuticsAuthor(s): John Henderson, Swati Bhattacharyya, John Varga, Steven O'ReillyAbstractSystemic sclerosis (SSc) is an idiopathic autoimmune disease characterised by inflammation, vascular problems, cytokine dysregulation and ultimately fibrosis, which accounts for poor prognosis and eventual mortality. At present no curative treatments exist, hence there is an urgent need to better understand the aetiology and develop improved therapies accordingly. Although still widely debated, significant evidence points to upregulation of the innate immu...
Source: Pharmacology and Therapeutics - August 4, 2018 Category: Drugs & Pharmacology Source Type: research

Prostaglandins in asthma and allergic diseases
Publication date: Available online 3 August 2018Source: Pharmacology & TherapeuticsAuthor(s): R. Stokes PeeblesAbstractProstaglandins are synthesized through the metabolism of arachidonic acid via the cyclooxygenase pathway. There are five primary prostaglandins, PGD2, PGE2, PGF2, PGI2, and thromboxane B2, that all signal through distinct seven transmembrane, G-protein coupled receptors. The receptor through which the prostaglandins signal determines their immunologic or physiologic effects. For instance, the same prostaglandin may have opposing properties, dependent upon the signaling pathways activated. In this artic...
Source: Pharmacology and Therapeutics - August 3, 2018 Category: Drugs & Pharmacology Source Type: research

Extracellular vesicles and their nucleic acids for biomarker discovery
Publication date: Available online 3 August 2018Source: Pharmacology & TherapeuticsAuthor(s): Fatemeh Momen-Heravi, Stephen J. Getting, Sterghios Athanasios MoschosAbstractExtracellular vesicles (EVs) are a heterogenous population of vesicles originate from cells. EVs are found in different biofluids and carry different macromolecules, including proteins, lipids, and nucleic acids, providing a snap shot of the parental cells at the time of release. EVs have the ability to transfer molecular cargoes to other cells and can initiate different physiological and pathological processes. Mounting lines of evidence demonstrate...
Source: Pharmacology and Therapeutics - August 3, 2018 Category: Drugs & Pharmacology Source Type: research

Editorial Board
Publication date: August 2018Source: Pharmacology & Therapeutics, Volume 188Author(s): (Source: Pharmacology and Therapeutics)
Source: Pharmacology and Therapeutics - July 30, 2018 Category: Drugs & Pharmacology Source Type: research

GPCR Regulation of Secretion
Publication date: Available online 26 July 2018Source: Pharmacology & TherapeuticsAuthor(s): Yun Young Yim, Zack Zurawski, Heidi HammAbstractModulation of neurotransmitter exocytosis by activated Gi/o coupled G-protein coupled receptors (GPCRs) is a universal regulatory mechanism used both to avoid overstimulation and to influence circuitry. One of the known modulation mechanisms is the interaction between Gβγ and the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNAREs). There are 5 Gβ and 12 Gγ subunits, but specific Gβγs activated by a given GPCR and the spec...
Source: Pharmacology and Therapeutics - July 27, 2018 Category: Drugs & Pharmacology Source Type: research

Endothelial function and dysfunction: impact of metformin
Publication date: Available online 27 July 2018Source: Pharmacology & TherapeuticsAuthor(s): Asma Nafisa, Susan G. Gray, Yingnan Cao, Tinghuai Wang, Suowen Xu, Feroza H. Wattoo, Michael Barras, Neale Cohen, Danielle Kamato, Peter J. LittleAbstractCardiovascular and metabolic diseases remain the leading cause of morbidity and mortality worldwide. Endothelial dysfunction is a key player in the initiation and progression of cardiovascular and metabolic diseases. Current evidence suggests that the anti-diabetic drug metformin improves insulin resistance and protects against endothelial dysfunction in the vasculature. Hereb...
Source: Pharmacology and Therapeutics - July 27, 2018 Category: Drugs & Pharmacology Source Type: research

Brown adipose tissue and lipid metabolism: New strategies for identification of activators and biomarkers with clinical potential
Publication date: Available online 24 July 2018Source: Pharmacology & TherapeuticsAuthor(s): Angie S. Xiang, Peter J. Meikle, Andrew L. Carey, Bronwyn A. KingwellAbstractDevelopment of therapeutic agents directed towards increasing brown adipose tissue (BAT) energy expenditure to combat obesity and its comorbidities is currently an area of intense research. Both preclinical and clinical studies have suggested a potentially significant role for BAT in regulating whole body energy expenditure as well as glucose and lipid metabolism. Lipids, particularly long chain fatty acids (LCFAs), are recognized as integral substrate...
Source: Pharmacology and Therapeutics - July 24, 2018 Category: Drugs & Pharmacology Source Type: research

20-hete in the regulation of vascular and cardiac function
Publication date: Available online 23 July 2018Source: Pharmacology & TherapeuticsAuthor(s): Petra Rocic, Michal Laniado SchwartzmanAbstract20-HETE, the ω-hydroxylation product of arachidonic acid catalyzed by enzymes of the cytochrome P450 (CYP) 4A and 4F gene families, is a bioactive lipid mediator with potent effects on the vasculature including stimulation of smooth muscle cell contractility, migration and proliferation as well as activation of endothelial cell dysfunction and inflammation. Clinical studies have shown elevated levels of plasma and urinary 20-HETE in human diseases and conditions such as hyper...
Source: Pharmacology and Therapeutics - July 24, 2018 Category: Drugs & Pharmacology Source Type: research