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Autism Spectrum disorder classification, diagnosis and therapy
Publication date: Available online 12 May 2018 Source:Pharmacology & Therapeutics Author(s): Samata R. Sharma, Xenia Gonda, Frank I. Tarazi Autism 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. Heredita...
Source: Pharmacology and Therapeutics - May 13, 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 2018 Source:Pharmacology & Therapeutics Author(s): Shun Chen, Chao Yang, Wei Zhang, Suresh Mahalingam, Mingshu Wang, Anchun Cheng Infections 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 conserve...
Source: Pharmacology and Therapeutics - May 7, 2018 Category: Drugs & Pharmacology Source Type: research

Autoimmune phenotypes in schizophrenia reveal novel treatment targets
Publication date: Available online 6 May 2018 Source:Pharmacology & Therapeutics Author(s): Emily G. Severance, Faith B. Dickerson, Robert H. Yolken Typical 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 centurie...
Source: Pharmacology and Therapeutics - May 6, 2018 Category: Drugs & Pharmacology Source Type: research

Clinical benefits and pharmacology of Scutellarin: A comprehensive review
Publication date: Available online 6 May 2018 Source:Pharmacology & Therapeutics Author(s): Liping Wang, Qiang Ma Stroke 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 ti...
Source: Pharmacology and Therapeutics - May 6, 2018 Category: Drugs & Pharmacology Source Type: research

Towards optimization of estrogen receptor modulation in medicine
Publication date: Available online 3 May 2018 Source:Pharmacology & Therapeutics Author(s): Marie-Cécile Valéra, Coralie Fontaine, Marion Dupuis, Emmanuelle Noirrit-Esclassan, Alexia Vinel, Maeva Guillaume, Pierre Gourdy, Françoise Lenfant, Jean-François Arnal Women 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), in...
Source: Pharmacology and Therapeutics - May 4, 2018 Category: Drugs & Pharmacology Source Type: research

ARID1A loss in Cancer: Towards a mechanistic understanding
Publication date: Available online 3 May 2018 Source:Pharmacology & Therapeutics Author(s): Radhika Mathur Genes 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 maint...
Source: Pharmacology and Therapeutics - May 4, 2018 Category: Drugs & Pharmacology Source Type: research

Mechanism of N6-methyladenosine Modification and Its Emerging Role in Cancer
Publication date: Available online 4 May 2018 Source:Pharmacology & Therapeutics Author(s): Sicong Zhang N 6-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 - May 4, 2018 Category: Drugs & Pharmacology Source Type: research

Therapeutic antibodies: A new era in the treatment of respiratory diseases?
Publication date: Available online 4 May 2018 Source:Pharmacology & Therapeutics Author(s): T. Sécher, L. Guilleminault, K. Reckamp, I. Amanam, L. Plantier, N. Heuzé-Vourc’h Respiratory 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 cur...
Source: Pharmacology and Therapeutics - May 4, 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 2018 Source:Pharmacology & Therapeutics Author(s): Torsten Schöneberg, Jaroslawna Meister, Alexander Bernd Knierim, Angela Schulz Research 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 m...
Source: Pharmacology and Therapeutics - May 1, 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 2018 Source:Pharmacology & Therapeutics Author(s): Shizuo Yamada, Yoshihiko Ito, Saori Nishijima, Katsumi Kadekawa, Kimio Sugaya Antimuscarinic 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 - April 28, 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 2018 Source:Pharmacology & Therapeutics Author(s): Joachim Alexandre, Javid Moslehi, Kevin R. Bersell, Christian Funck-Brentano, Dan M. Roden, Joe-Elie Salem Significant 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 heart...
Source: Pharmacology and Therapeutics - April 25, 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 2018 Source:Pharmacology & Therapeutics Author(s): Torsten Schöneberg, Jaroslawna Meister, Alexander Bernd Knierim, Angela Schulz Research 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 m...
Source: Pharmacology and Therapeutics - April 23, 2018 Category: Drugs & Pharmacology Source Type: research

Imaging techniques to study drug transporter function in vivo
Publication date: Available online 22 April 2018 Source:Pharmacology & Therapeutics Author(s): Nicolas Tournier, Bruno Stieger, Oliver Langer Transporter 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. Imaging...
Source: Pharmacology and Therapeutics - April 23, 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 2018 Source:Pharmacology & Therapeutics Author(s): Qinwei Yu, Zhenzhou Jiang, Luyong Zhang Non-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 - April 23, 2018 Category: Drugs & Pharmacology Source Type: research

Vitamin C for the treatment of Sepsis: The Scientific Rationale
Publication date: Available online 21 April 2018 Source:Pharmacology & Therapeutics Author(s): Paul E. Marik Most 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 model...
Source: Pharmacology and Therapeutics - April 22, 2018 Category: Drugs & Pharmacology Source Type: research

DNA Mismatch Repair in Cancer
Publication date: Available online 15 April 2018 Source:Pharmacology & Therapeutics Author(s): Marina Baretti, Dung T. Le Microsatellite 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 or...
Source: Pharmacology and Therapeutics - April 15, 2018 Category: Drugs & Pharmacology Source Type: research

Tools and drugs for uracil nucleotide-activated P2Y receptors
Publication date: Available online 13 April 2018 Source:Pharmacology & Therapeutics Author(s): Muhammad Rafehi, Christa E. Müller P2Y 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 famil...
Source: Pharmacology and Therapeutics - April 14, 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 - April 14, 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 2018 Source:Pharmacology & Therapeutics Author(s): Eleonora Leucci Cancer 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 human...
Source: Pharmacology and Therapeutics - April 10, 2018 Category: Drugs & Pharmacology Source Type: research

Extracellular vesicles as potential biomarkers for alcohol- and drug-induced liver injury and their therapeutic applications
Publication date: Available online 3 April 2018 Source:Pharmacology & Therapeutics Author(s): Young-Eun Cho, Byoung-Joon Song, Mohammed Akbar, Moon-Chang Baek Extracellular vesicles (EVs) are small membranous vesicles originating from various cells and tissues, including the liver parenchymal hepatocytes and nonparenchymal cells such as Kupffer and stellate cells. Recently, the pathophysiological role of EVs, such as exosomes and microvesicles, has been increasingly recognized based on intercellular communications. These EVs travel through the circulating blood and interact with specific cells and then deliver the...
Source: Pharmacology and Therapeutics - April 3, 2018 Category: Drugs & Pharmacology Source Type: research

Double-barreled gun: Combination of PARP inhibitor with conventional chemotherapy
Publication date: Available online 3 April 2018 Source:Pharmacology & Therapeutics Author(s): Yanxin Lu, Yang Liu, Ying Pang, Karel Pacak, Chunzhang Yang DNA 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 inhib...
Source: Pharmacology and Therapeutics - April 3, 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 2018 Source:Pharmacology & Therapeutics Author(s): Jan Christoph Koch, Lars Tatenhorst, Anna-Elisa Roser, Kim-Ann Saal, Lars Tönges, Paul Lingor Neurodegenerative 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 signific...
Source: Pharmacology and Therapeutics - April 3, 2018 Category: Drugs & Pharmacology Source Type: research

Arthropod toxins and their antinociceptive properties: From venoms to painkillers
Publication date: Available online 29 March 2018 Source:Pharmacology & Therapeutics Author(s): Victoria Monge-Fuentes, Claudia Arenas, Priscilla Galante, Jacqueline Coimbra Gonçalves, Márcia Renata Mortari, Elisabeth Ferroni Schwartz The 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 the...
Source: Pharmacology and Therapeutics - March 30, 2018 Category: Drugs & Pharmacology Source Type: research

Targeting the replication stress response in cancer
Publication date: Available online 24 March 2018 Source:Pharmacology & Therapeutics Author(s): Josep V. Forment, Mark J. O'Connor Many 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 broader DNA ...
Source: Pharmacology and Therapeutics - March 24, 2018 Category: Drugs & Pharmacology Source Type: research

Sirtuin activators and inhibitors: Promises, achievements, and challenges
Publication date: Available online 22 March 2018 Source:Pharmacology & Therapeutics Author(s): Han Dai, David A. Sinclair, James L. Ellis, Clemens Steegborn The 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 Sirt...
Source: Pharmacology and Therapeutics - March 23, 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 2018 Source:Pharmacology & Therapeutics Author(s): Danielle Gulick, Joshua J. Gamsby Although 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 disrupti...
Source: Pharmacology and Therapeutics - March 16, 2018 Category: Drugs & Pharmacology Source Type: research

Canine sarcomas as a surrogate for the human disease
Publication date: Available online 9 March 2018 Source:Pharmacology & Therapeutics Author(s): Daniel L. Gustafson, Dawn L. Duval, Daniel P. Regan, Douglas H. Thamm Pet 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 burden...
Source: Pharmacology and Therapeutics - March 10, 2018 Category: Drugs & Pharmacology Source Type: research

Discovery of Leonuri and therapeutical applications: From bench to bedside
Publication date: Available online 9 March 2018 Source:Pharmacology & Therapeutics Author(s): Yi Zhun Zhu, Weijun Wu, Qing Zhu, Xinhua Liu Despite 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 clinically...
Source: Pharmacology and Therapeutics - March 9, 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 2018 Source:Pharmacology & Therapeutics Author(s): Bridget Shafit-Zagardo, Ross C. Gruber, Juwen C. DuBois Tyro3, 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 re...
Source: Pharmacology and Therapeutics - March 5, 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 2018 Source:Pharmacology & Therapeutics Author(s): Michael J. Hurley, Robert M.J. Deacon, Katrin Beyer, Elena Ioannou, Agustin Ibáñez, Jessica L. Teeling, Patricia Cogram Alzheimer'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 - March 4, 2018 Category: Drugs & Pharmacology Source Type: research

CCRK is a novel signalling hub exploitable in cancer immunotherapy
Publication date: Available online 1 March 2018 Source:Pharmacology & Therapeutics Author(s): Myth T. Mok, Jingying Zhou, Wenshu Tang, Xuezhen Zeng, Antony W. Oliver, Simon E. Ward, Alfred S. Cheng Cyclin-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...
Source: Pharmacology and Therapeutics - March 2, 2018 Category: Drugs & Pharmacology Source Type: research

Newer Therapeutic Strategies for Soft-Tissue Sarcomas
Publication date: Available online 24 February 2018 Source:Pharmacology & Therapeutics Author(s): Kevin Bourcier, Antoine Italiano Metastatic 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:...
Source: Pharmacology and Therapeutics - February 24, 2018 Category: Drugs & Pharmacology Source Type: research

Nutraceuticals and osteoarthritis pain
Publication date: Available online 24 February 2018 Source:Pharmacology & Therapeutics Author(s): Angela Wang, Daniel J. Leong, Luis Cardoso, Hui B. Sun Arthritis is a chronic disease of joints. It is highly prevalent, particularly in the elderly, and is commonly associated with pain that interferes with quality of life. Because of its chronic nature, pharmacological approaches to pain relief and joint repair must be safe for long term use, a quality many current therapies lack. Nutraceuticals refer to compounds or materials that can function as nutrition and exert a potential therapeutic effect, including the rel...
Source: Pharmacology and Therapeutics - February 24, 2018 Category: Drugs & Pharmacology Source Type: research

Biogenesis and function of extracellular vesicles in cancer
Publication date: Available online 21 February 2018 Source:Pharmacology & Therapeutics Author(s): Maarten P. Bebelman, Martine J. Smit, D. Michiel Pegtel, S. Rubina Baglio Extracellular 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 biogen...
Source: Pharmacology and Therapeutics - February 21, 2018 Category: Drugs & Pharmacology Source Type: research

Inflammasome biology, molecular pathology and therapeutic implications
Publication date: Available online 18 February 2018 Source:Pharmacology & Therapeutics Author(s): Fawaz Awad, Eman Assrawi, Camille Louvrier, Claire Jumeau, Sophie Georgin-Lavialle, Gilles Grateau, Serge Amselem, Irina Giurgea, Sonia-Athina Karabina Inflammasomes are intracellular multiprotein signaling complexes, mainly present in myeloid cells. They commonly assemble around a cytoplasmic receptor of the nucleotide-binding leucine-rich repeat containing receptor (NLR) family, although other cytoplasmic receptors like pyrin have been shown to form inflammasomes. The nucleation of the multiprotein scaffolding platf...
Source: Pharmacology and Therapeutics - February 18, 2018 Category: Drugs & Pharmacology Source Type: research

WNT receptor signalling in lung physiology and pathology
Publication date: Available online 17 February 2018 Source:Pharmacology & Therapeutics Author(s): Wioletta Skronska-Wasek, Reinoud Gosens, Melanie Königshoff, Hoeke Abele Baarsma The WNT signalling cascades have emerged as critical regulators of a wide variety of biological aspects involved in lung development as well as in physiological and pathophysiological processes in the adult lung. WNTs (secreted glycoproteins) interact with various transmembrane receptors and co-receptors to activate signalling pathways that regulate transcriptional as well as non-transcriptional responses within cells. In physiologic...
Source: Pharmacology and Therapeutics - February 17, 2018 Category: Drugs & Pharmacology Source Type: research

Safer approaches to therapeutic modulation of TGF- β signaling for respiratory disease
Publication date: Available online 17 February 2018 Source:Pharmacology & Therapeutics Author(s): Philippe Lachapelle, Meina Li, Jo Douglass, Alastair Stewart The transforming growth factor (TGF)-β cytokines play a central role in development and progression of chronic respiratory diseases. TGF-β overexpression in chronic inflammation, remodeling, fibrotic process and susceptibility to viral infection is established in the most prevalent chronic respiratory diseases including asthma, COPD, lung cancer and idiopathic pulmonary fibrosis. Despite the overwhelming burden of respiratory diseases in the world,...
Source: Pharmacology and Therapeutics - February 17, 2018 Category: Drugs & Pharmacology Source Type: research

The relaxin receptor as a therapeutic target – perspectives from evolution and drug targeting
Publication date: Available online 17 February 2018 Source:Pharmacology & Therapeutics Author(s): Ross A.D. Bathgate, Martina Kocan, Daniel J. Scott, M. Akhter Hossain, Sara V. Good, Sergey Yegorov, Jan Bogerd, Paul Gooley The peptide relaxin was first identified as an important circulating hormone during pregnancy over 90 years ago. Research over many years defined the numerous biological roles that relaxin plays throughout pregnancy in many mammalian species. These important biological actions have led to the testing of relaxin as a therapeutic agent for a number of indications. The discovery of the relaxin rece...
Source: Pharmacology and Therapeutics - February 17, 2018 Category: Drugs & Pharmacology Source Type: research

Modulation of CYP1A1 metabolism: From adverse health effects to chemoprevention and therapeutic options
Publication date: Available online 17 February 2018 Source:Pharmacology & Therapeutics Author(s): Melina Mescher, Thomas Haarmann-Stemmann The human cytochrome P450 (CYP) 1A1 gene encodes a monooxygenase that metabolizes multiple exogenous and endogenous substrates. CYP1A1 has become infamous for its oxidative metabolism of benzo[a]pyrene and related polycyclic aromatic hydrocarbons, converting these chemicals into very potent human carcinogens. CYP1A1 expression is mainly controlled by the aryl hydrocarbon receptor (AHR), a transcription factor whose activation is induced by binding of persistent organic pollutan...
Source: Pharmacology and Therapeutics - February 17, 2018 Category: Drugs & Pharmacology Source Type: research

ERK1/2 inhibitors: New weapons to inhibit the RAS-regulated RAF-MEK1/2-ERK1/2 pathway
Publication date: Available online 16 February 2018 Source:Pharmacology & Therapeutics Author(s): Andrew M. Kidger, James Sipthorp, Simon J. Cook The RAS-regulated RAF-MEK1/2-ERK1/2 signalling pathway is de-regulated in a variety of cancers due to mutations in receptor tyrosine kinases (RTKs), negative regulators of RAS (such as NF1) and core pathway components themselves (RAS, BRAF, CRAF, MEK1 or MEK2). This has driven the development of a variety of pharmaceutical agents to inhibit RAF-MEK1/2-ERK1/2 signalling in cancer and both RAF and MEK inhibitors are now approved and used in the clinic. There is now much in...
Source: Pharmacology and Therapeutics - February 16, 2018 Category: Drugs & Pharmacology Source Type: research

Signalling pathways regulating galactosaminoglycan synthesis and structure in vascular smooth muscle: Implications for lipoprotein binding and atherosclerosis
Publication date: Available online 15 February 2018 Source:Pharmacology & Therapeutics Author(s): Rizwana Afroz, Yingnan Cao, Muhamad Ashraf Rostam, Hang Ta, Suowen Xu, Wenhua Zheng, Narin Osman, Danielle Kamato, Peter J. Little Atherosclerosis commences with the trapping of low density lipoproteins (LDLs) in blood vessels by modified proteoglycans (PGs) with hyperelongated glycosaminoglycan (GAG) chains. GAG chain synthesis and growth factor mediated hyperelongation regulates the composition and size of PGs in a manner that would cause low density lipoprotein (LDLs) retention in vessel wall. Galactosaminoglycans ...
Source: Pharmacology and Therapeutics - February 15, 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 2018 Source:Pharmacology & Therapeutics Author(s): Khushboo Agrawal, Viswanath Das, Pankhuri Vyas, Marián Hajdúch DNA 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 - February 15, 2018 Category: Drugs & Pharmacology Source Type: research

Circular RNA and its mechanisms in disease: From the bench to the clinic
Publication date: Available online 14 February 2018 Source:Pharmacology & Therapeutics Author(s): Bing Han, Jie Chao, Honghong Yao The emerging recognition of the functional roles of circular RNAs (circRNAs) has given rise to a new perspective regarding our understanding of cellular physiology and disease pathogenesis. Unlike linear RNAs, circRNAs are covalently closed continuous loops that act as gene regulators in mammals, and their sequence composition determines the mode of circRNA biogenesis. The availability and integrated use of advanced genome analysis platforms have allowed the identification of a large n...
Source: Pharmacology and Therapeutics - February 14, 2018 Category: Drugs & Pharmacology Source Type: research

Serelaxin as a novel therapeutic opposing fibrosis and contraction in lung diseases
Publication date: Available online 12 February 2018 Source:Pharmacology & Therapeutics Author(s): Maggie Lam, Simon G. Royce, Chrishan S. Samuel, Jane E. Bourke The most common therapies for asthma and other chronic lung diseases are anti-inflammatory agents and bronchodilators. While these drugs oppose disease symptoms, they do not reverse established structural changes in the airways and their therapeutic efficacy is reduced with increasing disease severity. The peptide hormone, relaxin, is a Relaxin Family Peptide Receptor 1 (RXFP1) receptor agonist with unique combined effects in the lung that differentiates i...
Source: Pharmacology and Therapeutics - February 12, 2018 Category: Drugs & Pharmacology Source Type: research

Efferocytosis in atherosclerotic lesions: Malfunctioning regulatory pathways and control mechanisms
Publication date: Available online 11 February 2018 Source:Pharmacology & Therapeutics Author(s): Amir Tajbakhsh, Mehdi Rezaee, Petri T. Kovanen, Amirhossein Sahebkar Atherosclerosis 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 a...
Source: Pharmacology and Therapeutics - February 11, 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: Available online 9 February 2018 Source:Pharmacology & Therapeutics Author(s): Yan-Yun Liu, Gregory A. Brent Thyroid 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 oc...
Source: Pharmacology and Therapeutics - February 9, 2018 Category: Drugs & Pharmacology Source Type: research

Targeting cancer stem cells in the clinic: Current status and perspectives
Publication date: Available online 5 February 2018 Source:Pharmacology & Therapeutics Author(s): Stephanie Annett, Tracy Robson Resistance to chemotherapy and cancer relapse are major clinical challenges attributed to a sub population of cancer stem cells (CSCs). The concept of CSCs has been the subject of intense research by the oncology community since evidence for their existence was first published over twenty years ago. Emerging data indicates that they are also able to evade novel therapies such as targeted agents, immunotherapies and anti-angiogenics. The inability to appropriately identify and isolate CSCs...
Source: Pharmacology and Therapeutics - February 5, 2018 Category: Drugs & Pharmacology Source Type: research

Evolving targets for the treatment of atherosclerosis
Publication date: Available online 4 February 2018 Source:Pharmacology & Therapeutics Author(s): Ankita Solanki, Lokesh Kumar Bhatt, Thomas P. Johnston Atherosclerosis is a progressive disease of large arteries and a leading cause of cardiovascular diseases and stroke. Chronic inflammation, aberrant immune response, and disturbances to key enzymes involved with lipid metabolism are characteristic features of atherosclerosis. Apart from targeting the derangements in lipid metabolism, therapeutic modulation to regulate chronic inflammation and the immune system response may prove to be very promising strategies in t...
Source: Pharmacology and Therapeutics - February 4, 2018 Category: Drugs & Pharmacology Source Type: research

Progress and challenges in deep brain stimulation for obsessive-compulsive disorder
Publication date: Available online 31 January 2018 Source:Pharmacology & Therapeutics Author(s): Sina Kohl, Juan C. Baldermann This 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 st...
Source: Pharmacology and Therapeutics - January 31, 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: Available online 31 January 2018 Source:Pharmacology & Therapeutics Author(s): Danielle O. Sambo, Joseph J. Lebowitz, Habibeh Khoshbouei Methamphetamine (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 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 &...
Source: Pharmacology and Therapeutics - January 31, 2018 Category: Drugs & Pharmacology Source Type: research