Updating Neuroimmune Targets in Central Nervous System Dysfunction.

abstract：:In the past 20 years we have learned a great deal about GABAA receptor (GABAAR) subtypes, and which behaviors are regulated or which drug effects are mediated by each subtype. However, the question of where GABAARs involved in specific drug effects and behaviors are located in the brain remains largely unanswered. We ...

journal_title：Trends in pharmacological sciences

authors： Engin E,Benham RS,Rudolph U

更新日期：2018-08-01 00:00:00

abstract：:Protease-activated receptors (PARs) are a ubiquitously expressed class of G-protein-coupled receptors (GPCRs) that enable cells to respond to proteases in the extracellular environment in a nuanced and dynamic manner. PAR1 is the archetypal family member and has been the object of large-scale drug development programs...

journal_title：Trends in pharmacological sciences

authors： Flaumenhaft R,De Ceunynck K

更新日期：2017-08-01 00:00:00

abstract：:Network and systems biology offer a novel way of approaching drug discovery by developing models that consider the global physiological environment of protein targets, and the effects of modifying them, without losing the key molecular details. Here we review some recent advances in network and systems biology applied...

journal_title：Trends in pharmacological sciences

authors： Pujol A,Mosca R,Farrés J,Aloy P

更新日期：2010-03-01 00:00:00

abstract：:Opioid receptors are expressed on peripheral sensory nerve endings, cutaneous cells, and immune cells; and local application of opioids is used for the treatment of inflammatory pain in arthritis, burns, skin grafts, and chronic wounds. However, peripherally active opioids can also directly modulate the inflammatory p...

journal_title：Trends in pharmacological sciences

authors： Stein C,Küchler S

更新日期：2013-06-01 00:00:00

abstract：:Schizophrenia is a grave psychiatric disorder with psychotic symptoms and an enigmatic etiology. Family studies have strongly indicated that genetic risk factors have a role in this disease. Recent findings, together with previously established evidence, highlight the PDZ-domain-containing protein interacting with C-k...

journal_title：Trends in pharmacological sciences

authors： Dev KK,Henley JM

更新日期：2006-11-01 00:00:00

abstract：:It is generally accepted that muscle wasting is caused by an increase in protein breakdown which seems to be associated with an ATP-dependent, non-lysosomal proteolytic system based on conjugation of proteins to the small polypeptide ubiquitin. Increases in ubiquitin conjugates and in ubiquitin mRNAs are found in the ...

journal_title：Trends in pharmacological sciences

authors： Argilés JM,López-Soriano FJ

更新日期：1996-06-01 00:00:00

abstract：:Recent studies in mice have identified single molecules that can delay multiple diseases of aging and extend lifespan. In theory, such molecules could prevent dozens of diseases simultaneously, potentially extending healthy years of life. In this review, we discuss recent advances, controversies, opportunities, and ch...

journal_title：Trends in pharmacological sciences

authors： Hubbard BP,Sinclair DA

更新日期：2014-03-01 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：: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：:During the past decade a great number of genes encoding high- and low-voltage-dependent Ca(2+) channels and their accessory subunits have been cloned. Studies of Ca(2+) channel structure-function relationships and channel regulation using cDNA expression in heterologous expression systems have revealed intricate detai...

journal_title：Trends in pharmacological sciences

authors： Muth JN,Varadi G,Schwartz A

更新日期：2001-10-01 00:00:00

abstract：:Transcription factors comprise just over 7% of the human proteome and serve as gatekeepers of cellular function, integrating external signal information into gene expression programs that reconfigure cellular physiology at the most basic levels. Surface-initiated cell signaling pathways converge on transcription facto...

journal_title：Trends in pharmacological sciences

authors： Filtz TM,Vogel WK,Leid M

更新日期：2014-02-01 00:00:00

abstract：:Humans are exposed to mixtures of chemicals, rather than to individual chemicals. From a public health point of view, it is most relevant to answer the question of whether or not the components in a mixture interact in a way that results in an increase in their overall effect compared with the sum of the effects of th...

journal_title：Trends in pharmacological sciences

authors： Groten JP,Feron VJ,Sühnel J

更新日期：2001-06-01 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：:Inappropriate production of the iron-regulatory hormone hepcidin contributes to the pathogenesis of common iron disorders. Absolute or relative deficiency of hepcidin causes iron overload in hereditary hemochromatosis and iron-loading anemias. Elevated hepcidin causes iron restriction in inflammatory conditions includ...

journal_title：Trends in pharmacological sciences

authors： Ruchala P,Nemeth E

更新日期：2014-03-01 00:00:00

abstract：:Since conformational flexibility, which is required for the function of a protein, comes at the expense of structural stability, many proteins, including G-protein-coupled receptors (GPCRs), are under constant risk of misfolding and aggregation. In this regard GPR37 (also named PAEL-R and ETBR-LP-1) takes a prominent ...

journal_title：Trends in pharmacological sciences

authors： Leinartaité L,Svenningsson P

更新日期：2017-08-01 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：:Until recently, release studies have failed to indicate the existence of autoreceptors on motor nerves. Ignaz Wessler now reports on a refinement of the technique - the measurement of newly synthesized [3H]acetylcholine released from the phrenic nerve - which provides clear evidence in support of release-modulating au...

journal_title：Trends in pharmacological sciences

authors： Wessler I

更新日期：1989-03-01 00:00:00

abstract：:Classical targeted drug discovery is based on targeting druggable targets, typically kinases and receptors of which the function can be agonized or antagonized. This strategy meets difficulties in cases such as Huntington's disease (HD) and similar neurodegenerative disorders, where the pathological function of the pr...

journal_title：Trends in pharmacological sciences

authors： Yu S,Liang Y,Palacino J,Difiglia M,Lu B

更新日期：2014-02-01 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：:Loss of function of the phosphatase and tensin homolog (PTEN) tumour suppressor contributes to the development of many cancers. However, in contrast to classical models of tumour suppression, partial loss of PTEN function appears to be frequently observed in the clinic. In addition, studies of both humans and mice wit...

journal_title：Trends in pharmacological sciences

authors： Leslie NR,Foti M

更新日期：2011-03-01 00:00:00

abstract：:It has taken 17 years from the first identification of a voltage-gated Ca2+ channel (CaV) beta-subunit as a band on a gel following purification of skeletal muscle dihydropyridine (DHP) receptors in 1987 to the publication of key information on the structures of Ca2+ channel beta-subunits. Three recent X-ray crystallo...

journal_title：Trends in pharmacological sciences

authors： Richards MW,Butcher AJ,Dolphin AC

更新日期：2004-12-01 00:00:00

abstract：:Ischaemia-reperfusion (I/R) injury is a common feature of several diseases associated with high morbidity and mortality, such as stroke and myocardial infarction. The damaged tissue displays cardinal signs of inflammation and microvascular injury that, unless resolved, lead to long-term tissue damage with associated d...

journal_title：Trends in pharmacological sciences

authors： Gavins FN

更新日期：2010-06-01 00:00:00

abstract：:Clodronate is a first-generation bisphosphonate used worldwide for antiresorptive therapy for osteoporosis. Although clodronate is analgesic in nature, its mechanism and efficacy were unknown for some time. Recently, clodronate was identified as a selective and potent inhibitor for vesicular nucleotide transporter (VN...

journal_title：Trends in pharmacological sciences

authors： Moriyama Y,Nomura M

更新日期：2018-01-01 00:00:00

abstract：:The sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of immunomodulatory receptors whose functions are regulated by their glycan ligands. Siglecs are attractive therapeutic targets because of their cell type-specific expression pattern, endocytic properties, high expression on certain lymphomas/l...

journal_title：Trends in pharmacological sciences

authors： Angata T,Nycholat CM,Macauley MS

更新日期：2015-10-01 00:00:00

abstract：:Receptors that are coupled to the production of inositol (1,4,5)-trisphosphate cause an increase in cytosolic free Ca2+ concentration as a consequence of both Ca2+ mobilization from intracellular stores and Ca2+ influx through the plasma membrane. Although this latter phenomenon appears attributable to the activation ...

journal_title：Trends in pharmacological sciences

authors： Fasolato C,Innocenti B,Pozzan T

更新日期：1994-03-01 00:00:00

abstract：:Changes in the structure and function of the small airways (<2mm diameter) are now recognized to play a major role in airflow limitation in both chronic obstructive pulmonary disease (COPD) and severe asthma. Increased thickness of the small airway wall causes lumenal narrowing, which can be further occluded by mucus ...

journal_title：Trends in pharmacological sciences

authors： Sturton G,Persson C,Barnes PJ

更新日期：2008-07-01 00:00:00

abstract：:The injectisome type three secretion system (T3SS) is a major virulence factor in Pseudomonas aeruginosa. This bacterium is responsible for severe infections in immunosuppressed or cystic fibrosis patients and has become resistant to many antibiotics. Inhibitors of T3SS may therefore constitute an innovative therapeut...

journal_title：Trends in pharmacological sciences

authors： Anantharajah A,Mingeot-Leclercq MP,Van Bambeke F

更新日期：2016-09-01 00:00:00

abstract：:Attempts to develop neuroprotective treatments for neurodegenerative disorders have not yet been clinically successful. Axonal degeneration has been recognized as a predominant driver of disability and disease progression in central nervous system (CNS) diseases such as amyotrophic lateral sclerosis (ALS), multiple sc...

journal_title：Trends in pharmacological sciences

authors： Krauss R,Bosanac T,Devraj R,Engber T,Hughes RO

更新日期：2020-04-01 00:00:00

abstract：:Current concepts of the mechanisms underlying many of the pharmacological effects of ethanol on the CNS involve disruption of ion channel function via the interaction of ethanol with specific hydrophobic sites on channel subunit proteins. Of particular clinical importance is the development of tolerance and dependence...

journal_title：Trends in pharmacological sciences

authors： Chandler LJ,Harris RA,Crews FT

更新日期：1998-12-01 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