Novel Therapeutic Targets for Managing Dyslipidemia.

abstract：:The vascular endothelium is a remarkably heterogeneous organ. In addition to well-characterized anatomical diversity in situ, specific differences are increasingly being recognized between surface antigens on endothelial cells from different tissues, including absence of the classic endothelial marker factor VIII-rela...

journal_title：Trends in pharmacological sciences

authors： McCarthy SA,Kuzu I,Gatter KC,Bicknell R

更新日期：1991-12-01 00:00:00

abstract：:Hypercontraction or abnormal contraction of vascular smooth muscle is a major cause of diseases such as hypertension and vasospasm of the coronary and cerebral arteries. A better understanding of the mechanism of regulation of smooth muscle contraction should lead to improved treatments for such diseases. Recent studi...

journal_title：Trends in pharmacological sciences

authors： Fukata Y,Amano M,Kaibuchi K

更新日期：2001-01-01 00:00:00

abstract：:K(+) channels are macromolecules embedded in biological membranes, where they play a key role in cellular excitability and signal transduction pathways. Knowledge of their structure should help improve our understanding of their function and lead to the design of therapeutic compounds. Most pharmacological and structu...

journal_title：Trends in pharmacological sciences

authors： Rodríguez de la Vega RC,Merino E,Becerril B,Possani LD

更新日期：2003-05-01 00:00:00

abstract：:Neuronal Ca2+-sensor (NCS) proteins constitute a subfamily of closely related EF-hand Ca2+-binding proteins that are expressed mainly in neurons or retinal photoreceptor cells. A variety of different neuronal functions have been attributed to these proteins. However, important new discoveries indicate that these prote...

journal_title：Trends in pharmacological sciences

authors： Braunewell KH

更新日期：2005-07-01 00:00:00

abstract：:The use of genetically-engineered mice has identified alpha2- and alpha3-subunit containing GABA(A) receptors as principal contributors to the spinal disinhibition that occurs after inflammation and neuropathic injury. Pharmacological comparison of subtype selective allosteric modulators such as NS11394 and L838417 wi...

journal_title：Trends in pharmacological sciences

authors： Munro G,Ahring PK,Mirza NR

更新日期：2009-09-01 00:00:00

abstract：:For more than 30 years, WNT/β-catenin and planar cell polarity signaling has formed the basis for what we understand to be the primary output of the interaction between WNTs and their cognate receptors known as Frizzleds (FZDs). In the shadow of these pathways, evidence for the involvement of heterotrimeric G proteins...

journal_title：Trends in pharmacological sciences

authors： Schulte G,Wright SC

更新日期：2018-09-01 00:00:00

abstract：:Hypertension is prevalent and affects approximately 1 in every 4 adults in the Western world. Although many drugs are effective in treating hypertension, an individual's response to treatment is unpredictable. Pharmacogenetics holds the promise of becoming a tool to predict this response but obstacles and shortcomings...

journal_title：Trends in pharmacological sciences

authors： Kurland L,Lind L,Melhus H

更新日期：2005-09-01 00:00:00

abstract：:Approximately 27 million people are living with a tumour in which the tumour suppressing activity of p53 has been inactivated. In half of these tumours, p53 itself is not mutated but the pathway is partially abrogated. Mechanisms include the overexpression of negative regulators of p53, such as MDM2 and MDM4, and dele...

journal_title：Trends in pharmacological sciences

authors： Brown CJ,Cheok CF,Verma CS,Lane DP

更新日期：2011-01-01 00:00:00

abstract：:The importance of the inhibitory neurotransmitter, GABA, within higher centres of the mammalian brain is unquestionable. However, its role within the spinal cord is of equal significance. There have been numerous studies over the past two decades that have established GABA as a neurotransmitter at both post- and presy...

journal_title：Trends in pharmacological sciences

authors： Malcangio M,Bowery NG

更新日期：1996-12-01 00:00:00

abstract：:Antipsychotic drugs (APDs), and the 'atypical' APDs in particular, are commonly associated with metabolic side effects in humans. These include glucose dysregulation, insulin resistance, hyperlipidemia, weight gain and hypertension, which put patients at increased risk of cardiometabolic disorders. The underlying biol...

journal_title：Trends in pharmacological sciences

authors： Boyda HN,Tse L,Procyshyn RM,Honer WG,Barr AM

更新日期：2010-10-01 00:00:00

abstract：:Amyotrophic lateral sclerosis (ALS) is an incurable disease that arises from the progressive loss of motoneurons. Even when caused by a single gene defect, as in the case of mutations in the enzyme Cu-Zn superoxide dismutase (SOD1), ALS is the result of a complex cascade that involves crosstalk among motoneurons, glia...

journal_title：Trends in pharmacological sciences

authors： Carrì MT,Grignaschi G,Bendotti C

更新日期：2006-05-01 00:00:00

abstract：:Within the past six months, isolation of cDNA or genomic clones has been reported for three 5-HT receptors, the 5-HT1C, 5-HT1A and 5-HT2 subtypes. As members of the G protein receptor superfamily, all three 5-HT receptor clones encode single-subunit proteins containing approximately 450 amino acids arrayed as seven in...

journal_title：Trends in pharmacological sciences

authors： Hartig PR

更新日期：1989-02-01 00:00:00

abstract：:For almost 70 years, children have received stimulants for the treatment of attention deficit hyperactivity disorder [ADHD (initially called hyperkinetic syndrome)], with little understanding of the long-term effects of these drugs on brain development. The maturation and refinement of the brain during childhood and a...

journal_title：Trends in pharmacological sciences

authors： Andersen SL

更新日期：2005-05-01 00:00:00

abstract：:It has been suggested that G protein-coupled receptors can act as proton transporters, with the activated G protein-coupled receptor transporting H+ across the membrane from the extracellular side to the cytoplasm. In this article, Paul Nederkoorn, Henk Timmerman and Gabriëlle Donné-Op den Kelder summarize the various...

journal_title：Trends in pharmacological sciences

authors： Nederkoorn PH,Timmerman H,Donné-Op den Kelder GM

更新日期：1995-05-01 00:00:00

abstract：:Glucocorticosteroids are highly effective in controlling inflammation and the molecular mechanisms involved are now becoming clear. Activation of glucocorticoid receptors results in increased or decreased transcription of a number of genes involved in the inflammatory process. Of particular importance is the repressio...

journal_title：Trends in pharmacological sciences

authors： Barnes PJ,Adcock I

更新日期：1993-12-01 00:00:00

abstract：:G protein-coupled receptors (GPCRs) comprise a large and diverse class of signal-transducing receptors that undergo dynamic and isoform-specific membrane trafficking. GPCRs thus have an inherent potential to initiate or regulate signaling reactions from multiple membrane locations. This review discusses emerging insig...

journal_title：Trends in pharmacological sciences

authors： Eichel K,von Zastrow M

更新日期：2018-02-01 00:00:00

abstract：:Addiction biology has focused on the mechanisms of the positive and negative reinforcing actions of addictive drugs but neglected potential benefits. Two new studies provide the first insights into a neurobiology of psychoactive drug instrumentalization. This may help us design better models for addiction neuroscience...

journal_title：Trends in pharmacological sciences

authors： Müller CP,Kornhuber J

更新日期：2017-06-01 00:00:00

abstract：:The metabotropic glutamate (mGlu) receptors are a family of G-protein-coupled receptors (GPCRs) that regulate cell physiology throughout the nervous system. The potential of mGlu receptors as therapeutic targets has been bolstered by current research that has provided insight into the diverse modes of mGlu activation ...

journal_title：Trends in pharmacological sciences

authors： Stansley BJ,Conn PJ

更新日期：2019-04-01 00:00:00

abstract：:Protein engineering is a powerful tool for studying relationships between receptor structure and function--providing that it is used and interpreted appropriately. Site-directed mutagenesis, deletion mutagenesis and construction of chimaeric proteins have all been used to characterize receptors. In this review, Walter...

journal_title：Trends in pharmacological sciences

authors： Ward WH,Timms D,Fersht AR

更新日期：1990-07-01 00:00:00

abstract：:Several lines of evidence suggest that adenosine may be an endogenous protective agent in cerebral ischaemia. Adenosine is normally present in the extracellular fluid in most tissues of the body, including the brain, and its level increases dramatically following hypoxia or ischaemia. The rate of adenosine production ...

journal_title：Trends in pharmacological sciences

authors： Rudolphi KA,Schubert P,Parkinson FE,Fredholm BB

更新日期：1992-12-01 00:00:00

abstract：:The genotoxicity of the most potent carcinogen in cigarette smoke [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)] is dependent on the relationship between its activation by cytochrome P450 enzymes and its detoxification by carbonyl reduction to NNK alcohol (NNAL) followed by glucuronidation. Recently, '11 beta-...

journal_title：Trends in pharmacological sciences

authors： Maser E

更新日期：1997-08-01 00:00:00

abstract：:Drug development consumes huge amounts of time and money and the search for novel analgesics, which are urgently required, is particularly difficult, having resulted in many setbacks in the past. Drug repurposing - the identification of new uses for existing drugs - is an alternative approach, which bypasses most of t...

journal_title：Trends in pharmacological sciences

authors： Sisignano M,Parnham MJ,Geisslinger G

更新日期：2016-03-01 00:00:00

abstract：:Within five years of discovering endothelin (ET-1) in 1988, the first report of an orally available ET receptor antagonist was published. Within twelve years, bosentan, the first ET receptor antagonist to gain marketing authorization, was made available for the treatment of pulmonary artery hypertension (PAH). Since t...

journal_title：Trends in pharmacological sciences

authors： Dhaun N,Pollock DM,Goddard J,Webb DJ

更新日期：2007-11-01 00:00:00

abstract：:The therapeutic advantage of reducing the activity of interleukin 1 (IL-1) resides in preventing its deleterious biological effects without interfering with homeostasis. As such, methods attempting to block the production or activity of IL-1 have now entered clinical trials. For example, IL-1 induction of prostaglandi...

journal_title：Trends in pharmacological sciences

authors： Dinarello CA

更新日期：1993-05-01 00:00:00

abstract：:Since G protein-coupled receptors (GPCRs) belong to a very large superfamily of evolutionarily related receptors (>800 members in humans), and due to the rapid progress on their structural biology, they are ideal candidates for polypharmacology studies. Broad screening and bioinformatics/chemoinformatics have been app...

journal_title：Trends in pharmacological sciences

authors： Jacobson KA,Costanzi S,Paoletta S

更新日期：2014-12-01 00:00:00

abstract：:Intercellular transfer of proteins is a mode of communication between cells that is crucial for certain physiological processes. Chemotherapy is the treatment of choice for approximately 50% of all cancers. However, multidrug resistance mediated by drug-efflux pumps such as P-glycoprotein (Pgp) minimizes the effective...

journal_title：Trends in pharmacological sciences

authors： Ambudkar SV,Sauna ZE,Gottesman MM,Szakacs G

更新日期：2005-08-01 00:00:00

abstract：:Data sets from recent large-scale projects can be integrated into one unified puzzle that can provide new insights into how drugs and genetic perturbations applied to human cells are linked to whole-organism phenotypes. Data that report how drugs affect the phenotype of human cell lines and how drugs induce changes in...

journal_title：Trends in pharmacological sciences

authors： Ma'ayan A,Rouillard AD,Clark NR,Wang Z,Duan Q,Kou Y

更新日期：2014-09-01 00:00:00

abstract：:The potent pro-inflammatory cytokines tumour necrosis factor alpha (TNF-alpha) and interleukin 1 (IL-1) are capable of triggering biologically similar effects through activation of the same set of transcription factors. Based on recent findings it is now becoming evident that certain members of the mitogen-activated p...

journal_title：Trends in pharmacological sciences

authors： Eder J

更新日期：1997-09-01 00:00:00

abstract：:Over the past few decades, mortality resulting from cardiovascular disease (CVD) steadily decreased in western countries; however, in recent years, the decline has become offset by the increase in obesity. Obesity is strongly associated with the metabolic syndrome and its atherogenic dyslipidemia resulting from insuli...

journal_title：Trends in pharmacological sciences

authors： Soyal SM,Nofziger C,Dossena S,Paulmichl M,Patsch W

更新日期：2015-06-01 00:00:00

abstract：:Cytochrome P450 3A (CYP3A) enzymes metabolize a wide variety of xenobiotics including many drugs. Because CYP3A is localized in both the liver and intestine, it can make a major contribution to the presystemic elimination of substrate drugs after oral administration ('first-pass metabolism'). However, assessments of t...

journal_title：Trends in pharmacological sciences

authors： van Herwaarden AE,van Waterschoot RA,Schinkel AH

更新日期：2009-05-01 00:00:00