Abstract：
:Current medicines for the clinical management of inflammatory diseases act by inhibiting specific enzymes or antagonising specific receptors or blocking their ligands. In the past decade, a new paradigm in our understanding of the inflammatory process has emerged with the appreciation of genetic, molecular, and cellular mechanisms that are engaged to actively resolve inflammation. The 'resolution of acute inflammation' is enabled by counter-regulatory checkpoints to terminate the inflammatory reaction, promoting healing and repair. It may be possible to harness this knowledge for innovative approaches to the treatment of inflammatory pathologies. Here we discuss current translational attempts to develop agonists at proresolving targets as a strategy to rectify chronic inflammatory status. We reason this new approach will lead to the identification of better drugs that will establish a new branch of pharmacology, 'resolution pharmacology'.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Perretti M,Leroy X,Bland EJ,Montero-Melendez Tdoi
10.1016/j.tips.2015.07.007subject
Has Abstractpub_date
2015-11-01 00:00:00pages
737-755issue
11eissn
0165-6147issn
1873-3735pii
S0165-6147(15)00157-1journal_volume
36pub_type
杂志文章,评审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
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(00)01797-1
更新日期：2001-10-01 00:00:00
abstract：:Muscarinic acetylcholine receptor subtypes m1, m3 and m5 couple strongly to phosphatidylinositol turnover and hence to intracellular Ca2+ concentration via pertussis toxin (PTX) sensitive and insensitive G proteins. The m2 and m4 muscarinic receptor subtypes strongly inhibit adenylyl cyclase production via PTX sensiti...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：
更新日期：1989-12-01 00:00:00
abstract：:In drug development, major resources are invested into the development of cellular delivery systems to increase the effectiveness of a large array of potential therapeutics, such as proteins and oligonucleotides. These carriers comprise cell-penetrating peptides (CPPs), cationic lipids and cationic polymers. In recent...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2010.11.005
更新日期：2011-02-01 00:00:00
abstract：:Recently, nicotinic acid adenine dinucleotide phosphate (NAADP) has been shown, using different techniques, to mobilize intracellular Ca2+ stores in invertebrate, lower vertebrate, plant and mammalian cells. This endogenous molecule might play an atypical role in Ca2+ signalling by coordinating the responses of other ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(00)01990-8
更新日期：2002-04-01 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
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(00)01720-x
更新日期：2001-06-01 00:00:00
abstract：:In the discipline of pharmacology, drugs (ligands) are used as tools to elucidate the processes of biological systems. Because of this, pharmacologists strive to delineate all characteristics of drugs. Decades of research have resulted in the proposal that ligands possess two properties that are intrinsic to the ligan...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(97)01138-3
更新日期：1998-07-01 00:00:00
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
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(91)90637-8
更新日期：1991-12-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2010.12.005
更新日期：2011-03-01 00:00:00
abstract：:Endothelial-dependent relaxation of vascular smooth muscle cells evoked by a number of agonists, including cholinomimetics and substance P, is often accompanied by an increase (repolarization and/or hyperpolarization) in the membrane potential. This change in membrane potential appears predominantly to reflect the act...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(00)88969-5
更新日期：1995-01-01 00:00:00
abstract：:Recent developments in genetic research using Saccharomyces cerevisiae have provided rapid new methods for identifying the genes that control cellular responses to treatment with a wide variety of agents, including chemicals and radiation. This significantly increases the power of yeast as a model system for studying ...
journal_title：Trends in pharmacological sciences
pub_type： 新闻
doi：10.1016/s0165-6147(02)02082-5
更新日期：2002-10-01 00:00:00
abstract：:Toll-like receptors (TLRs) play a crucial role in innate immunity by recognizing conserved motifs predominantly found in microorganisms. Increasing evidence supports a role for TLRs in sterile inflammation as observed in neurodegenerative disorders. This includes work suggesting a contribution for these receptors to t...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2012.07.002
更新日期：2012-10-01 00:00:00
abstract：:Cys loop, glutamate, and P2X receptors are ligand-gated ion channels (LGICs) with 5, 4, and 3 protomers, respectively. There is now growing atomic level understanding of their gating mechanisms. Although each family is unique in the architecture of the ligand-binding pocket, the pathway for motions to propagate from l...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2012.06.005
更新日期：2012-09-01 00:00:00
abstract：:Clinical experience with muscarinic agonists in the symptomatic treatment of Alzheimer's disease includes studies of the effects of pilocarpine, arecoline, bethanechol, oxotremorine and RS 86. Although the results are somewhat conflicting, there is evidence that a subgroup of patients may respond with an improvement o...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：
更新日期：1989-12-01 00:00:00
abstract：:Heat shock proteins (HSPs) constitute a large family of proteins involved in protein folding and maturation whose expression is induced by heat shock or other stressors. The major groups are classified based on their molecular weights and include HSP27, HSP40, HSP60, HSP70, HSP90, and large HSPs. HSPs play a significa...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2016.11.009
更新日期：2017-03-01 00:00:00
abstract：:The affinity of a drug candidate for a biological membrane (its lipophilicity) is closely related to the pharmacologically crucial events of absorption, biodistribution, metabolization and excretion. The evolution of knowledge of biological membranes during the past two decades contrasts with the rudimentary parameter...
journal_title：Trends in pharmacological sciences
pub_type： 历史文章,杂志文章
doi：10.1016/j.tips.2010.06.007
更新日期：2010-10-01 00:00:00
abstract：:Nearly all molecules known to signal cells via G proteins have been assigned a cloned G-protein-coupled-receptor (GPCR) gene. This has been the result of a decade-long genetic search that has also identified some receptors for which ligands are unknown; these receptors are described as orphans (oGPCRs). More than 80 o...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(99)01366-8
更新日期：1999-09-01 00:00:00
abstract：:Evidence of off-target effects (OTEs) associated with small interfering (si)RNAs (19-29bp) in mammalian cells has existed for several years. Two recent articles demonstrate that short sequences within long double-stranded (ds)RNAs frequently cause undesirable OTEs in cultured Drosophila cells. These results reveal the...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2007.02.009
更新日期：2007-04-01 00:00:00
abstract：:Tissue factor (TF) is the cellular receptor and cofactor for blood coagulation factor VII (FVII). Exposure of flowing blood to cells that express TF leads to the initiation of blood coagulation. A recent study of mice expressing low levels of TF has demonstrated the importance of TF and FVII in maintaining adequate ha...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/S0165-6147(03)00121-4
更新日期：2003-06-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2017.05.001
更新日期：2017-08-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2010.04.001
更新日期：2010-06-01 00:00:00
abstract：:Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the Methyl CpG binding protein 2 (MeCP2) gene. This Science & Society article focuses on pharmacological strategies that attack RTT treatment from multiple angles, including drug repurposing and de novo discovery efforts, and discusses the imp...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2019.02.007
更新日期：2019-04-01 00:00:00
abstract：:The NLRP3 inflammasome is an intracellular multimeric protein complex which plays an important role in the pathogenesis of various human inflammatory diseases, such as diabetes, Alzheimer's disease and atherosclerosis. Recently, various G protein-coupled receptors (GPCRs) have been reported to be involved in the activ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2018.07.002
更新日期：2018-09-01 00:00:00
abstract：:Bioluminescence resonance energy transfer has developed in recent years as a new technique to study protein-protein interactions. Protein partners of interest are tagged with either luciferase or green fluorescent protein (GFP). Non-radiative energy transfer between the excited luciferase and the GFP permits the study...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(02)02062-x
更新日期：2002-08-01 00:00:00
abstract：:Drugs that cause liver injury often 'stress' mitochondria and activate signal transduction pathways important in determining cell survival or death. In most cases, hepatocytes adapt to the drug-induced stress by activating adaptive signaling pathways, such as mitochondrial adaptive responses and nuclear factor erythro...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2013.01.009
更新日期：2013-04-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2017.11.009
更新日期：2018-02-01 00:00:00
abstract：:Thiol-based drugs are considered as mucolytics because they decrease the viscosity and mostly decrease the elasticity of bronchial secretions by reducing disulfide bonds in proteins. However, they can also act as antioxidant drugs directly through free sulfhydryl groups that serve as a source of reducing equivalents, ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2019.04.015
更新日期：2019-07-01 00:00:00
abstract：:Multidrug resistance is associated with the overexpression of P-glycoprotein, a membrane glycoprotein. The mechanism by which P-glycoprotein confers to cells the capacity to resist cytotoxic attack by structurally unrelated drugs has remained difficult to decipher. However, the recent functional expression of this gro...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(94)90322-0
更新日期：1994-07-01 00:00:00
abstract：:Controversy over the meaning of pharmacological parameters often arises because of a lack of appreciation of different hierarchical levels of analysis. In a recent letter in Trends in Pharmacological Sciences, Zhang and Kavana [1] concluded that my two-state model for allosterism lacks cooperativity, even though Figur...
journal_title：Trends in pharmacological sciences
pub_type： 评论,信件
doi：10.1016/j.tips.2016.06.001
更新日期：2016-08-01 00:00:00
abstract：:Kinin B1 and B2 receptors are central to the aetiology of pain and inflammation. Constitutive B2 receptors are commonly associated with the acute phase of inflammation and nociception, whereas the inducible B1 receptors are mostly linked to the chronic or persistent phase (or both). Therefore, selective, orally active...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2006.10.007
更新日期：2006-12-01 00:00:00
abstract：:Inter-organelle signaling plays important roles in many physiological functions. Endoplasmic reticulum (ER)-mitochondrion signaling affects intramitochondrial calcium (Ca(2+)) homeostasis and cellular bioenergetics. ER-nucleus signaling attenuates ER stress. ER-plasma membrane signaling regulates cytosolic Ca(2+) home...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2010.08.007
更新日期：2010-12-01 00:00:00
