Mitochondrial Ca2+ signaling
Publication date: Available online 20 July 2018Source: Pharmacology & TherapeuticsAuthor(s): Trayambak Pathak, Mohamed TrebakAbstractMitochondrial Ca2+ regulation is crucial for bioenergetics and cellular signaling. The mechanisms controlling mitochondrial calcium homeostasis have been recently unraveled with the discovery of mitochondrial inner membrane proteins that regulate mitochondrial Ca2+ uptake and extrusion. Mitochondrial Ca2+ uptake depends on a large complex of proteins centered around the Ca2+ channel protein, mitochondrial Ca2+ uniporter (MCU) in close interactions with several regulatory subunits (MCUb, E...
Source: Pharmacology and Therapeutics - July 21, 2018 Category: Drugs & Pharmacology Source Type: research

Neurosteroids: non-genomic pathways in neuroplasticity and involvement in neurological diseases
Publication date: Available online 25 June 2018Source: Pharmacology & TherapeuticsAuthor(s): Marina Schverer, Laurence Lanfumey, Etienne-Emile Baulieu, Nicolas Froger, Isabelle VilleyAbstractNeurosteroids are neuroactive brain-born steroids. They can act through non-genomic and/or through genomic pathways. Genomic pathways are largely described for steroid hormones: the binding to nuclear receptors leads to transcription regulation. Pregnenolone, Dehydroepiandrosterone, their respective sulfate esters and Allopregnanolone have no corresponding nuclear receptor identified so far whereas some of their non-genomic targets...
Source: Pharmacology and Therapeutics - July 13, 2018 Category: Drugs & Pharmacology Source Type: research

Efferocytosis in atherosclerotic lesions: Malfunctioning regulatory pathways and control mechanisms
Publication date: Available online 11 February 2018Source: Pharmacology & TherapeuticsAuthor(s): Amir Tajbakhsh, Mehdi Rezaee, Petri T. Kovanen, Amirhossein SahebkarAbstractAtherosclerosis is a dynamic and progressive inflammatory process in the intimal layer of large and medium-sized arteries, and it is the major contributor to the atherosclerotic cardiovascular disease (ACVD), the leading cause of death worldwide. In an atherosclerotic plaque, phagocytosis of apoptotic cells occurs through an intricate process designated efferocytosis. Defective efferocytosis has emerged as a causal factor in the etiopathogenesis of ...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Nucleosidic DNA demethylating epigenetic drugs – A comprehensive review from discovery to clinic
Publication date: Available online 15 February 2018Source: Pharmacology & TherapeuticsAuthor(s): Khushboo Agrawal, Viswanath Das, Pankhuri Vyas, Marián HajdúchAbstractDNA methylation plays a pivotal role in the etiology of cancer by mediating epigenetic silencing of cancer-related genes. Since the relationship between aberrant DNA methylation and cancer has been understood, there has been an explosion of research at developing anti-cancer therapies that work by inhibiting DNA methylation. From the discovery of first DNA hypomethylating drugs in the 1980s to recently discovered second generation pro-drugs,...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Biogenesis and function of extracellular vesicles in cancer
Publication date: Available online 21 February 2018Source: Pharmacology & TherapeuticsAuthor(s): Maarten P. Bebelman, Martine J. Smit, D. Michiel Pegtel, S. Rubina BaglioAbstractExtracellular vesicles (EVs) are heterogeneous multi-signal messengers that support cancer growth and dissemination by mediating the tumor-stroma crosstalk. Exosomes are a subtype of EVs that originate from the limiting membrane of late endosomes, and as such contain information linked to both the intrinsic cell “state” and the extracellular signals cells received from their environment. Resolving the signals affecting exosome bioge...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Newer therapeutic strategies for soft-tissue sarcomas
Publication date: Available online 24 February 2018Source: Pharmacology & TherapeuticsAuthor(s): Kevin Bourcier, Antoine ItalianoAbstractMetastatic soft-tissue sarcoma (STS), a devastating disease, has a median overall survival of only 12–18 months. Until recently, therapeutic options were limited and relied primarily on the use of anthracycline-based chemotherapy. Over the past two decades, improvement in the knowledge of the biology of STS has allowed the investigation of new therapeutic strategies including new cytotoxic agents, epigenetic drugs, specific targeted therapies, and immunotherapeutic treatments....
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

The long-lived Octodon degus as a rodent drug discovery model for Alzheimer's and other age-related diseases
Publication date: Available online 4 March 2018Source: Pharmacology & TherapeuticsAuthor(s): Michael J. Hurley, Robert M.J. Deacon, Katrin Beyer, Elena Ioannou, Agustin Ibáñez, Jessica L. Teeling, Patricia CogramAbstractAlzheimer's disease (AD) is a multifactorial progressive neurodegenerative disease. Despite decades of research, no disease modifying therapy is available and a change of research objectives and/or development of novel research tools may be required. Much AD research has been based on experimental models using animals with a short lifespan that have been extensively genetically manipulated...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

The role of TAM family receptors and ligands in the nervous system: From development to pathobiology
Publication date: Available online 4 March 2018Source: Pharmacology & TherapeuticsAuthor(s): Bridget Shafit-Zagardo, Ross C. Gruber, Juwen C. DuBoisAbstractTyro3, Axl, and Mertk, referred to as the TAM family of receptor tyrosine kinases, are instrumental in maintaining cell survival and homeostasis in mammals. TAM receptors interact with multiple signaling molecules to regulate cell migration, survival, phagocytosis and clearance of metabolic products and cell debris called efferocytosis. The TAMs also function as rheostats to reduce the expression of proinflammatory molecules and prevent autoimmunity. All three TAM r...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Canine sarcomas as a surrogate for the human disease
Publication date: Available online 9 March 2018Source: Pharmacology & TherapeuticsAuthor(s): Daniel L. Gustafson, Dawn L. Duval, Daniel P. Regan, Douglas H. ThammAbstractPet dogs are becoming increasingly recognized as a population with the potential to inform medical research through their treatment for a variety of maladies by veterinary health professionals. This is the basis of the One Health initiative, supporting the idea of collaboration between human and animal health researchers and clinicians to study spontaneous disease processes and treatment in animals to inform human health. Cancer is a major health burde...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Discovery of Leonuri and therapeutical applications: From bench to bedside
Publication date: Available online 9 March 2018Source: Pharmacology & TherapeuticsAuthor(s): Yi Zhun Zhu, Weijun Wu, Qing Zhu, Xinhua LiuAbstractDespite several advances in percutaneous coronary intervention and the discovery of new drugs, the incidence of myocardial infarction and deaths due to cardiovascular diseases (CVD) has not decreased markedly in China. The quality of life is affected seriously, which further results in great social and family burden. Many drugs, from the century-old aspirin to the newly FDA-approved Byvalson, have been proven to be effective in the treatment and prevention of CVD. As clinicall...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Racing the clock: The role of circadian rhythmicity in addiction across the lifespan
Publication date: Available online 15 March 2018Source: Pharmacology & TherapeuticsAuthor(s): Danielle Gulick, Joshua J. GamsbyAbstractAlthough potent effects of psychoactive drugs on circadian rhythms were first described over 30 years ago, research into the reciprocal relationship between the reward system and the circadian system – and the impact of this relationship on addiction – has only become a focus in the last decade. Nonetheless, great progress has been made in that short time toward understanding how drugs of abuse impact the molecular and physiological circadian clocks, as well as how disrupt...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Sirtuin activators and inhibitors: Promises, achievements, and challenges
Publication date: Available online 22 March 2018Source: Pharmacology & TherapeuticsAuthor(s): Han Dai, David A. Sinclair, James L. Ellis, Clemens SteegbornAbstractThe NAD+-dependent protein lysine deacylases of the Sirtuin family regulate various physiological functions, from energy metabolism to stress responses. The human Sirtuin isoforms, SIRT1–7, are considered attractive therapeutic targets for aging-related diseases, such as type 2 diabetes, inflammatory diseases and neurodegenerative disorders. We review the status of Sirtuin-targeted drug discovery and development. Potent and selective pharmacological Sir...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Targeting the replication stress response in cancer
Publication date: Available online 24 March 2018Source: Pharmacology & TherapeuticsAuthor(s): Josep V. Forment, Mark J. O’ConnorAbstractMany conventional chemotherapies used in cancer treatment exert their effect by inflicting DNA damage. Highly proliferative tissues, as well as tumour cells, are particularly vulnerable to this damage resulting in unwanted toxicities. In contrast, a targeted therapeutic approach has the aim of specifically eliminating cancer cells but with a reduced effect on healthy tissue. New therapies have been developed that target the replication stress response (RSR), a branch of the broad...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Arthropod toxins and their antinociceptive properties: From venoms to painkillers
Publication date: Available online 29 March 2018Source: Pharmacology & TherapeuticsAuthor(s): Victoria Monge-Fuentes, Claudia Arenas, Priscilla Galante, Jacqueline Coimbra Gonçalves, Márcia Renata Mortari, Elisabeth Ferroni SchwartzAbstractThe complex process of pain control commonly involves the use of systemic analgesics; however, in many cases, a more potent and effective polypharmacological approach is needed to promote clinically significant improvement. Additionally, considering side effects caused by current painkillers, drug discovery is once more turning to nature as a source of more efficient th...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

ROCK inhibition in models of neurodegeneration and its potential for clinical translation
Publication date: Available online 3 April 2018Source: Pharmacology & TherapeuticsAuthor(s): Jan Christoph Koch, Lars Tatenhorst, Anna-Elisa Roser, Kim-Ann Saal, Lars Tönges, Paul LingorAbstractNeurodegenerative disorders like Parkinson's disease, Alzheimer's disease, or amyotrophic lateral sclerosis are affecting a rapidly increasing population worldwide. While common pathomechanisms such as protein aggregation, axonal degeneration, dysfunction of protein clearing and an altered immune response have been characterized, no disease-modifying therapies have been developed so far. Interestingly, a significant involve...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Double-barreled gun: Combination of PARP inhibitor with conventional chemotherapy
Publication date: Available online 3 April 2018Source: Pharmacology & TherapeuticsAuthor(s): Yanxin Lu, Yang Liu, Ying Pang, Karel Pacak, Chunzhang YangAbstractDNA repair pathways are evolutionarily conserved molecular mechanisms that maintain the integrity of genomic DNA. In cancer therapies, the integrity and activity of DNA repair pathways predict therapy resistance and disease outcome. Members of the poly (ADP-ribose) polymerase (PARP) family initiate and organize the biologic process of DNA repair, which counteracts many types of chemotherapies. Since the first development in approximately 3 decades ago, PARP inhi...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Cancer development and therapy resistance: spotlights on the dark side of the genome
Publication date: Available online 10 April 2018Source: Pharmacology & TherapeuticsAuthor(s): Eleonora LeucciAbstractCancer research has been focusing so far on genetic alterations in protein-coding genes. However, mounting evidence underlines the importance of epigenetic and post-transcriptional events in cancer progression and therapy resistance. Moreover, recent genome-wide studies show that disease-causing mutations and chromosome rearrangements often span areas of the genome that do not contain any known protein-coding gene. This finding is not surprising, considering that even though the vast majority of the huma...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Natural killer cells and their therapeutic role in pancreatic cancer: A systematic review
In conclusion, although several issues regarding NK cells in pancreatic cancer remain unsolved and need further investigation, extensive evidence is already provided that support NK cell oriented approaches in pancreatic cancer. (Source: Pharmacology and Therapeutics)
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Tools and drugs for uracil nucleotide-activated P2Y receptors
Publication date: Available online 13 April 2018Source: Pharmacology & TherapeuticsAuthor(s): Muhammad Rafehi, Christa E. MüllerAbstractP2Y receptors (P2YRs) are a family of G protein-coupled receptors activated by extracellular nucleotides. Physiological P2YR agonists include purine and pyrimidine nucleoside di- and triphosphates, such as ATP, ADP, UTP, UDP, nucleotide sugars, and dinucleotides. Eight subtypes exist, P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14, which represent current or potential future drug targets. Here we provide a comprehensive overview of ligands for the subgroup of the P2YR fami...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

DNA mismatch repair in cancer
Publication date: Available online 15 April 2018Source: Pharmacology & TherapeuticsAuthor(s): Marina Baretti, Dung T. LeAbstractMicrosatellite instability (MSI) refers to the hypermutator phenotype secondary to frequent polymorphism in short repetitive DNA sequences and single nucleotide substitution, as consequence of DNA mismatch repair (MMR) deficiency. MSI secondary to germline mutation in DNA MMR proteins is the molecular fingerprint of Lynch syndrome (LS), while epigenetic inactivation of these genes is more commonly found in sporadic MSI tumors. MSI occurs at different frequencies across malignancies, although o...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Vitamin C for the treatment of sepsis: The scientific rationale
Publication date: Available online 21 April 2018Source: Pharmacology & TherapeuticsAuthor(s): Paul E. MarikAbstractMost vertebrates can synthesize vitamin C with synthesis increasing during stress. Humans, however, have lost the ability to synthesize vitamin C. Vitamin C is an important anti-oxidant and an enzyme cofactor for many important biological reactions. Sepsis results in the overwhelming production of reactive oxygen species with widespread endothelial, cellular and mitochondrial injury leading to progressive organ failure. Sepsis is associated with an acute deficiency of vitamin C. In experimental sepsis mode...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

The G protein-coupled receptor GPR34 – The past 20 years of a grownup
Publication date: Available online 22 April 2018Source: Pharmacology & TherapeuticsAuthor(s): Torsten Schöneberg, Jaroslawna Meister, Alexander Bernd Knierim, Angela SchulzAbstractResearch on GPR34, which was discovered in 1999 as an orphan G protein-coupled receptor of the rhodopsin-like class, disclosed its physiologic relevance only piece by piece. Being present in all recent vertebrate genomes analyzed so far it seems to improve the fitness of species although it is not essential for life and reproduction as GPR34-deficient mice demonstrate. However, closer inspection of macrophages and microglia, where it is ...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Imaging techniques to study drug transporter function in vivo
Publication date: Available online 22 April 2018Source: Pharmacology & TherapeuticsAuthor(s): Nicolas Tournier, Bruno Stieger, Oliver LangerAbstractTransporter systems involved in the permeation of drugs and solutes across biological membranes are recognized as key determinants of pharmacokinetics. Typically, the action of membrane transporters on drug exposure to tissues in living organisms is inferred from invasive procedures, which cannot be applied in humans. In recent years, imaging methods have greatly progressed in terms of instruments, synthesis of novel imaging probes as well as tools for data analysis. Imagin...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Bile acid regulation: A novel therapeutic strategy in non-alcoholic fatty liver disease
Publication date: Available online 22 April 2018Source: Pharmacology & TherapeuticsAuthor(s): Qinwei Yu, Zhenzhou Jiang, Luyong ZhangAbstractNon-alcoholic fatty liver disease (NAFLD) is characterized by excessive fat deposition in the liver in the absence of significant alcohol consumption. Dysregulated bile acid (BA) metabolism is an important indicator in the pathology of NAFLD, which could progress into more severe forms of liver injury. Lipid metabolism, immune environment and intestinal bacteria are all affected by dysregulated BA metabolism directly, but the mechanisms remain unclear. Several drug candidates that...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Anticancer drug-induced cardiac rhythm disorders: Current knowledge and basic underlying mechanisms
Publication date: Available online 24 April 2018Source: Pharmacology & TherapeuticsAuthor(s): Joachim Alexandre, Javid J. Molsehi, Kevin R. Bersell, Christian Funck-Brentano, Dan M. Roden, Joe-Elie SalemAbstractSignificant advances in cancer treatment have resulted in decreased cancer related mortality for many malignancies with some cancer types now considered chronic diseases. Despite these improvements, there is increasing recognition that many cancer patients or cancer survivors can develop cardiovascular diseases, either due to the cancer itself or as a result of anticancer therapy. Much attention has focused on h...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Basic and clinical aspects of antimuscarinic agents used to treat overactive bladder
Publication date: Available online 27 April 2018Source: Pharmacology & TherapeuticsAuthor(s): Shizuo Yamada, Yoshihiko Ito, Saori Nishijima, Katsumi Kadekawa, Kimio SugayaAbstractAntimuscarinic agents are now widely used as the pharmacological therapy for overactive bladder (OAB) because neuronal (parasympathetic nerve) and non-neuronal acetylcholine play a significant role for the bladder function. In this review, we will highlight basic and clinical aspects of eight antimuscarinic agents (oxybutynin, propiverine, tolterodine, solifenacin, darifenacin, trospium, imidafenacin, and fesoterodine) clinically used to treat...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Towards optimization of estrogen receptor modulation in medicine
Publication date: Available online 3 May 2018Source: Pharmacology & TherapeuticsAuthor(s): Marie-Cécile Valéra, Coralie Fontaine, Marion Dupuis, Emmanuelle Noirrit-Esclassan, Alexia Vinel, Maeva Guillaume, Pierre Gourdy, Françoise Lenfant, Jean-François ArnalAbstractWomen now spend more than one-third of their lives in the postmenopausal years, and the decline of endogenous estrogen production during menopause is accompanied by a series of functional disorders that affect the quality of life. These symptoms could be alleviated or even totally suppressed by menopausal hormone therapy (MHT), i...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

ARID1A loss in cancer: Towards a mechanistic understanding
Publication date: Available online 3 May 2018Source: Pharmacology & TherapeuticsAuthor(s): Radhika MathurAbstractGenes encoding subunits of SWI/SNF chromatin remodeling complexes are collectively mutated in 20% of all human cancers. ARID1A is the SWI/SNF subunit gene that is most frequently mutated, at variable frequencies across molecular and histological subtypes of cancer. Mouse modeling has revealed that the role of ARID1A in tumor suppression is highly dependent upon context. Recent mechanistic studies have identified a crucial role for ARID1A in targeting SWI/SNF complexes to tissue-specific enhancers and in main...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Therapeutic antibodies: A new era in the treatment of respiratory diseases?
Publication date: Available online 4 May 2018Source: Pharmacology & TherapeuticsAuthor(s): T. Sécher, L. Guilleminault, K. Reckamp, I. Amanam, L. Plantier, N. Heuzé-Vourc'hAbstractRespiratory diseases affect millions of people worldwide, and account for significant levels of disability and mortality. The treatment of lung cancer and asthma with therapeutic antibodies (Abs) is a breakthrough that opens up new paradigms for the management of respiratory diseases. Antibodies are becoming increasingly important in respiratory medicine; dozens of Abs have received marketing approval, and many more are currentl...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Mechanism of N6-methyladenosine Modification and Its Emerging Role in Cancer
Publication date: Available online 4 May 2018Source: Pharmacology & TherapeuticsAuthor(s): Sicong ZhangAbstractN6-methyladenosine (m6A), the most prevalent internal methylation in messenger RNA (mRNA) that is deposited by m6A methyltransferases, removed by m6A demethylases and recognized by different RNA-binding proteins, distinguishes the transcripts through multilayer interactions with mRNA processing, export, degradation and translation machineries. m6A plays an important role in regulation of gene expression for fundamental cellular processes and diverse physiological functions. Aberrant m6A decorations lead to can...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Autoimmune phenotypes in schizophrenia reveal novel treatment targets
Publication date: Available online 6 May 2018Source: Pharmacology & TherapeuticsAuthor(s): Emily G. Severance, Faith B. Dickerson, Robert H. YolkenAbstractTypical and atypical antipsychotics are the first-line treatments for schizophrenia, but these classes of drugs are not universally effective, and they can have serious side effects that impact compliance. Antipsychotic drugs generally target the dopamine pathways with some variation. As research of schizophrenia pathophysiology has shifted away from a strictly dopamine-centric focus, the development of new pharmacotherapies has waned. A field of inquiry with centuri...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Flaviviridae virus nonstructural proteins 5 and 5A mediate viral immune evasion and are promising targets in drug development
Publication date: Available online 6 May 2018Source: Pharmacology & TherapeuticsAuthor(s): Shun Chen, Chao Yang, Wei Zhang, Suresh Mahalingam, Mingshu Wang, Anchun ChengAbstractInfections with viruses in the Flaviviridae family have a vast global and economic impact because of the high morbidity and mortality. The pathogenesis of Flaviviridae infections is very complex and not fully understood because these viruses can inhibit multiple immune pathways including the complement system, NK cells, and IFN induction and signalling pathways. The non-structural (NS) 5 and 5A proteins of Flaviviridae viruses are highly conserv...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Clinical benefits and pharmacology of scutellarin: A comprehensive review
Publication date: Available online 6 May 2018Source: Pharmacology & TherapeuticsAuthor(s): Liping Wang, Qiang MaAbstractStroke and myocardial infarction are among the most common causes of mortality and disability in the world. The ischemic injury underlying these illnesses is complex, involving intricate interplays among many biological functions including energy metabolism, vascular regulation, hemodynamics, oxidative stress, inflammation, platelet activation, and tissue repair that take place in a context- and time-dependent manner. The current drug therapy of choice is to timely resupply the blood to the ischemic t...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Autism Spectrum Disorder: Classification, diagnosis and therapy
Publication date: Available online 12 May 2018Source: Pharmacology & TherapeuticsAuthor(s): Samata R. Sharma, Xenia Gonda, Frank I. TaraziAbstractAutism Spectrum Disorder (ASD) refers to a group of neurodevelopmental disorders including autism, Asperger's syndrome (AS) and pervasive developmental disorder-not otherwise specified (PDD-NOS). The new diagnostic criteria of ASD focuses on two core domains: social communication impairment and restricted interests/repetitive behaviors. The prevalence of ASD has been steadily increasing over the past two decades, with current estimates reaching up to 1 in 36 children. Heredit...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Prenatal inflammation exposure-programmed cardiovascular diseases and potential prevention
Publication date: Available online 25 May 2018Source: Pharmacology & TherapeuticsAuthor(s): Youcai Deng, Liang Song, Xuqiang Nie, Weinian Shou, Xiaohui LiAbstractIn recent years, the rapid development of medical and pharmacological interventions has led to a steady decline in certain noncommunicable chronic diseases (NCDs), such as cancer. However, the overall incidence of cardiovascular diseases (CVDs) has not seemed to decline. CVDs have become even more prevalent in many countries and represent a global health threat and financial burden. An increasing number of epidemiological and experimental studies have demonstr...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

The neurobiology of depression, ketamine and rapid-acting antidepressants: Is it glutamate inhibition or activation?
Publication date: Available online 25 May 2018Source: Pharmacology & TherapeuticsAuthor(s): Chadi G. Abdallah, Gerard Sanacora, Ronald S. Duman, John H. KrystalAbstractThe discovery of the antidepressant effects of ketamine has opened a breakthrough opportunity to develop a truly novel class of safe, effective, and rapid-acting antidepressants (RAADs). In addition, the rapid and robust biological and behavioral effects of ketamine offered a unique opportunity to utilize the drug as a tool to thoroughly investigate the neurobiology of stress and depression in animals, and to develop sensitive and reproducible biomarkers...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Vascular effects of apelin: Mechanisms and therapeutic potential
Publication date: Available online 25 May 2018Source: Pharmacology & TherapeuticsAuthor(s): Amreen Mughal, Stephen T. O'RourkeAbstractApelin is a vasoactive peptide and is an endogenous ligand for APJ receptors, which are widely expressed in blood vessels, heart, and cardiovascular regulatory regions of the brain. A growing body of evidence now demonstrates a regulatory role for the apelin/APJ receptor system in cardiovascular physiology and pathophysiology, thus making it a potential target for cardiovascular drug discovery and development. Indeed, ongoing studies are investigating the potential benefits of apelin and...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Advances in stroke pharmacology
Publication date: Available online 25 May 2018Source: Pharmacology & TherapeuticsAuthor(s): Zhenhua Zhou, Jianfei Lu, Wen-Wu Liu, Anatol Manaenko, Xianhua Hou, Qiyong Mei, Jun-Long Huang, Jiping Tang, John H. Zhang, Honghong Yao, Qin HuAbstractStroke occurs when a cerebral blood vessel is blocked or ruptured, and it is the major cause of death and adult disability worldwide. Various pharmacological agents have been developed for the treatment of stroke either through interrupting the molecular pathways leading to neuronal death or enhancing neuronal survival and regeneration. Except for rtPA, few of these agents have s...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Therapeutic targeting of cathepsin C: from pathophysiology to treatment
Publication date: Available online 26 May 2018Source: Pharmacology & TherapeuticsAuthor(s): Brice Korkmaz, George H. Caughey, Iain Chapple, Francis Gauthier, Josefine Hirschfeld, Dieter E. Jenne, Ralph Kettritz, Gilles Lalmanach, Anne-Sophie Lamort, Conni Lauritzen, Monika Łȩgowska, Adam Lesner, Sylvain Marchand-Adam, Sarah J. McKaig, Celia Moss, John Pedersen, Helen Roberts, Adrian Schreiber, Seda Seren, Nalin S. ThakkerAbstractCathepsin C (CatC) is a highly conserved tetrameric lysosomal cysteine dipeptidyl aminopeptidase. The best characterized physiological function of CatC is the activation of pro-inflammatory g...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Pharmacological modulation of the CO2/HCO3−/pH-, calcium-, and ATP-sensing soluble adenylyl cyclase
Publication date: Available online 26 May 2018Source: Pharmacology & TherapeuticsAuthor(s): Shakarr V. Wiggins, Clemens Steegborn, Lonny R. Levin, Jochen BuckAbstractCyclic AMP (cAMP), the prototypical second messenger, has been implicated in a wide variety of (often opposing) physiological processes. It simultaneously mediates multiple, diverse processes, often within a single cell, by acting locally within independently-regulated and spatially-restricted microdomains. Within each microdomain, the level of cAMP will be dependent upon the balance between its synthesis by adenylyl cyclases and its degradation by phospho...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs) in cancer treatment
Publication date: June 2018Source: Pharmacology & Therapeutics, Volume 186Author(s): Hitisha K. Patel, Teeru BihaniAbstractBreast cancer is the most frequently diagnosed cancer in women, with estrogen receptor positive (ER+) breast cancer making up approximately 75% of all breast cancers diagnosed. Given the dependence on active ER signaling in these tumors, the predominant treatment strategy has been to inhibit various aspects of this pathway including directly antagonizing ER with the use of selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs). Interestingly, the dependence...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

The Hippo pathway in normal development and cancer
Publication date: June 2018Source: Pharmacology & Therapeutics, Volume 186Author(s): Marcello Maugeri-Saccà, Ruggero De MariaAbstractThe Hippo pathway is a central regulator of organ size and tissue homeostasis. Hippo kinases and adaptor proteins mediate the phosphorylation and inactivation of YAP and TAZ, two closely related transcription co-activators. The Hippo pathway responds to a variety of extracellular and intracellular signals, spanning from cell-cell contact and mechanical cues to ligands of G-protein-coupled receptors and metabolic avenues. In some instances, YAP/TAZ activation is tuned by forces that...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Which place of pharmacological approaches beyond continuous positive airway pressure to treat vascular disease related to obstructive sleep apnea?
Publication date: June 2018Source: Pharmacology & Therapeutics, Volume 186Author(s): Elodie Gautier-Veyret, Jean-Louis Pépin, Françoise Stanke-LabesqueAbstractObstructive sleep apnea (OSA) is characterized by recurrent episodes of partial or complete upper airway obstruction, occurring during sleep, leading to chronic intermittent hypoxia (IH), which harms the cardiovascular system. OSA is associated with both functional and structural vascular alterations that contribute to an increased prevalence of fatal and non-fatal cardiovascular events. OSA is a heterogeneous disease with respect to the severity of...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Chronopathophysiological implications of orexin in sleep disturbances and lifestyle-related disorders
Publication date: June 2018Source: Pharmacology & Therapeutics, Volume 186Author(s): Hiroshi Tsuneki, Tsutomu Wada, Toshiyasu SasaokaAbstractSleep, a mysterious behavior, has recently been recognized as a crucial factor for health and longevity. The daily sleep/wake cycle provides the basis of biorhythms controlling whole-body homeostasis and homeodynamics; therefore, disruption of sleep causes several physical and psychological disorders, including cardiovascular disease, obesity, diabetes, cancer, anxiety, depression, and cognitive dysfunction. However, the mechanism linking sleep disturbances and sleep-related disor...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Editorial Board
Publication date: June 2018Source: Pharmacology & Therapeutics, Volume 186Author(s): (Source: Pharmacology and Therapeutics)
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Thyroid hormone and the brain: Mechanisms of action in development and role in protection and promotion of recovery after brain injury
Publication date: June 2018Source: Pharmacology & Therapeutics, Volume 186Author(s): Yan-Yun Liu, Gregory A. BrentAbstractThyroid hormone (TH) is essential for normal brain development and may also promote recovery and neuronal regeneration after brain injury. TH acts predominantly through the nuclear receptors, TH receptor alpha (THRA) and beta (THRB). Additional factors that impact TH action in the brain include metabolism, activation of thyroxine (T4) to triiodothyronine (T3) by the enzyme 5′-deiodinase Type 2 (Dio2), inactivation by the enzyme 5-deiodinase Type 3 (Dio3) to reverse T3 (rT3), which occurs in gl...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Progress and challenges in deep brain stimulation for obsessive-compulsive disorder
Publication date: June 2018Source: Pharmacology & Therapeutics, Volume 186Author(s): Sina Kohl, Juan Carlos BaldermannAbstractThis narrative review summarizes the recent literature on deep brain stimulation for treatment resistant obsessive-compulsive disorder highlighting both progress and challenges of this novel treatment. Common targets of psychiatric deep brain stimulation involve both white matter trajectories (anterior limb of the internal capsule, inferior thalamic peduncle, and medial forebrain bundle) and grey matter subcortical nuclei (nucleus accumbens, nucleus subthalamicus, and bed nucleus of the stria te...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

The sigma-1 receptor as a regulator of dopamine neurotransmission: A potential therapeutic target for methamphetamine addiction
Publication date: June 2018Source: Pharmacology & Therapeutics, Volume 186Author(s): Danielle O. Sambo, Joseph J. Lebowitz, Habibeh KhoshboueiAbstractMethamphetamine (METH) abuse is a major public health issue around the world, yet there are currently no effective pharmacotherapies for the treatment of METH addiction. METH is a potent psychostimulant that increases extracellular dopamine levels by targeting the dopamine transporter (DAT) and alters neuronal activity in the reward centers of the brain. One promising therapeutic target for the treatment of METH addiction is the sigma-1 receptor (σ1R). The σ1R...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

CCRK is a novel signalling hub exploitable in cancer immunotherapy
Publication date: June 2018Source: Pharmacology & Therapeutics, Volume 186Author(s): Myth T. Mok, Jingying Zhou, Wenshu Tang, Xuezhen Zeng, Antony W. Oliver, Simon E. Ward, Alfred S. ChengAbstractCyclin-dependent kinase 20 (CDK20), or more commonly referred to as cell cycle-related kinase (CCRK), is the latest member of CDK family with strong linkage to human cancers. Accumulating studies have reported the consistent overexpression of CCRK in cancers arising from brain, colon, liver, lung and ovary. Such aberrant up-regulation of CCRK is clinically significant as it correlates with tumor staging, shorter patient surviv...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Combining chemotherapy with PD-1 blockade in NSCLC
Publication date: June 2018Source: Pharmacology & Therapeutics, Volume 186Author(s): Matthen Mathew, Thomas Enzler, Catherine A. Shu, Naiyer A. RizviAbstractAntitumor immunity relies on the ability of the immune system to recognize tumor cells as foreign and eliminate them. An effective immune response in this setting is due to surveillance of tumor-specific antigens that induce an adaptive immune response resulting in T-cell mediated cytotoxicity. Immune checkpoint inhibitors, specifically those targeting the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis, have demonstrated promising activi...
Source: Pharmacology and Therapeutics - July 10, 2018 Category: Drugs & Pharmacology Source Type: research