Abstract：
:The purpose of this Opinion is to present a case for targeting sphingosine kinase 2 (SK2) in autoimmune/inflammatory disease. Data obtained using Sphk2-/- mice suggest that SK2 is an anti-inflammatory enzyme, although this might be misleading because of a compensatory increase in the expression of a second isoform, sphingosine kinase 1 (SK1), which functions as a proinflammatory enzyme. SK2 is involved in regulating interleukin (IL)-12/interferon gamma (IFN-γ) and histone deacetylase-1/2 (HDAC-1/2) signalling and, potentially, retinoid-related orphan receptor gamma t (ROR-γt) stability linked with T helper (Th) 17 cell polarisation. Therefore, there is a need to develop highly potent SK2 inhibitors with selectivity over SK1 to clearly define the role of SK2 in autoimmune/inflammatory disease. Structural determinants of SK2 relative to SK1 will enable the design of selective SK2 inhibitors.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Pyne NJ,Adams DR,Pyne Sdoi
10.1016/j.tips.2017.04.003subject
Has Abstractpub_date
2017-07-01 00:00:00pages
581-591issue
7eissn
0165-6147issn
1873-3735pii
S0165-6147(17)30095-0journal_volume
38pub_type
杂志文章,评审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
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(97)01090-0
更新日期：1997-08-01 00:00:00
abstract：:Recent studies have proposed a functional link between annexin 1 (ANXA1), an endogenous anti-inflammatory mediator, and receptors of the formyl-peptide family. In particular, exogenous and endogenous ANXA1 and its peptidomimetics interact with one member of this family, the formyl-peptide-receptor-like 1. Further anal...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2003.09.010
更新日期：2003-11-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2018.08.004
更新日期：2018-11-01 00:00:00
abstract：:Degradation of heme requires its conversion to biliverdin (BV) by heme oxygenase, followed by reduction of BV to the free-radical quencher bilirubin (BR) by biliverdin reductase (BVR). It is now recognized that human BVR (hBVR) is a dual-specificity kinase (Ser/Thr and Tyr) upstream activator of the insulin/insulin gr...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2008.12.003
更新日期：2009-03-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2013.09.004
更新日期：2013-11-01 00:00:00
abstract：:Oxidative stress is a key pathologic factor in neurodegenerative diseases such as Alzheimer and Parkinson diseases (AD, PD). The failure of free-radical-scavenging antioxidants in clinical trials pinpoints an urgent need to identify and to block major sources of oxidative stress in neurodegenerative diseases. As a maj...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2012.03.008
更新日期：2012-06-01 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
abstract：:cGMP inhibits hypertrophy, decreases fibrosis, and protects against cardiac ischemia-reperfusion (I/R) injury. Gene-targeting studies have not defined a clear role for its major downstream effector, cGMP-dependent protein kinase I (cGKI), in cardiac hypertrophy, but do implicate cGMP-cGKI signaling in fibrosis and I/R...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2014.05.003
更新日期：2014-08-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2007.01.006
更新日期：2007-03-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2007.01.002
更新日期：2007-03-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2019.02.006
更新日期：2019-04-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/s0165-6147(99)01428-5
更新日期：2000-02-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2015.07.007
更新日期：2015-11-01 00:00:00
abstract：:Recent molecular cloning studies have identified several genes encoding alpha and beta subunits of the nicotinic acetylcholine receptor. These genes have distinct, although overlapping, patterns of expression in the brain and peripheral ganglia. Multiple nicotinic receptors with distinct pharmacological and functional...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(91)90486-c
更新日期：1991-01-01 00:00:00
abstract：:Centrally acting drugs interfere with the function of central neurotransmitter systems. This often requires intact neuronal connections and is therefore best studied in vivo. Here, Gaetano Di Chiara describes the technique of brain dialysis, which permits direct in-vivo sampling of neurotransmitters and their metaboli...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(90)90197-g
更新日期：1990-03-01 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：: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
pub_type： 杂志文章
doi：10.1016/j.tips.2005.07.008
更新日期：2005-09-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(93)90064-Q
更新日期：1993-11-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
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更新日期：2000-05-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2014.12.001
更新日期：2015-02-01 00:00:00
abstract：:Annexin A1 (ANXA1) is an endogenous protein known to have potent anti-inflammatory properties in the peripheral system. It has also been detected in the brain, but its function there is still ambiguous. In this review, we have, for the first time, collated the evidence currently available on the function of ANXA1 in t...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2007.12.003
更新日期：2008-03-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2020.12.004
更新日期：2021-01-23 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
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更新日期：2002-08-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2005.03.009
更新日期：2005-05-01 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
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(90)90009-w
更新日期：1990-07-01 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
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(97)01097-3
更新日期：1997-09-01 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：:Dimerization is fairly common in the G-protein-coupled receptor (GPCR) superfamily. First attempts to rationalize this phenomenon gave rise to an idea that two receptors in a dimer could be necessary to bind a single molecule of G protein or arrestin. Although GPCRs, G proteins and arrestins were crystallized only in ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2008.02.004
更新日期：2008-05-01 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
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(98)01268-1
更新日期：1998-12-01 00:00:00
abstract：:Cyclic AMP (cAMP) steers the generation of basal heart beat in the sinoatrial node. It also induces sinoatrial tachycardia and increased cardiac force, elicited through activation of Gs-protein-coupled receptors (GsPCRs). Phosphodiesterases (PDEs) hydrolyse cAMP. In the heart mainly PDE3 and PDE4 would be expected to ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2011.03.003
更新日期：2011-07-01 00:00:00
