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::B7x (B7 homolog x, also known as B7-H4, B7S1, and VTCN1) was discovered by ourselves and others in 2003 as the seventh member of the B7 family. It is an inhibitory immune checkpoint of great significance to human disease. Tissue-expressed B7x minimizes autoimmune and inflammatory responses. It is overexpressed in a br...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2019.09.008
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abstract::Muscarinic agonists open potassium-selective K(ACh) channels in cardiac myocytes of pacemaker or atrial origin. Receptor activation is coupled to channel opening by a membrane bound guanine nucleotide-binding protein (GK) through a process that does not require cytoplasmic intermediates. We have used the muscarinic po...
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::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::Cancer initiates at one site (primary tumor) and, in most cases, spreads to other distant organs (metastasis). During the multistep process of metastasis, primary tumor cells acquire cellular and phenotypic plasticity to survive and thrive in different environments. Moreover, cancer cells also utilize and educate micr...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2019.04.005
更新日期:2019-06-01 00:00:00
abstract::Oxycodone is a semisynthetic opioid analgesic that is increasingly used for the treatment of acute, cancer, and chronic non-malignant pain. Oxycodone was synthesized in 1917 but its pharmacological properties were not thoroughly studied until recently. Oxycodone is a fairly selective μ-opioid receptor agonist, but the...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2013.02.001
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abstract::Recent advances in schizophrenia (SZ) research indicate that the telencephalic gamma-aminobutyric acid (GABA)ergic neurotransmission deficit associated with this psychiatric disorder probably is mediated by the hypermethylation of the glutamic acid decarboxylase 67 (GAD(67)), reelin and other GABAergic promoters. A ph...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2008.10.010
更新日期:2009-02-01 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
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更新日期:2002-08-01 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::The metabotropic glutamate type 7 (mglu(7)) receptor is a widely distributed, mainly presynaptic Group III mglu receptor that can regulate glutamate release. Recently, largely as a result of the identification of specific proteins that interact with the C-terminal domain of this receptor, considerable progress has bee...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(00)01684-9
更新日期:2001-07-01 00:00:00
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journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2005.07.007
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
doi:10.1016/s0165-6147(99)01428-5
更新日期:2000-02-01 00:00:00
abstract::Platelet activating factor (PAF) is a phospholipid mediator of inflammation and stimulates anion secretion in animals and in isolated preparations of human colon. Nitric oxide (NO), synthesized from the amino acid L-arginine, is an important enteric inhibitory neurotransmitter. In addition, NO-donating compounds stimu...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(98)01249-8
更新日期:1998-10-01 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::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
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(92)90141-r
更新日期:1992-12-01 00:00:00
abstract::Mechanisms of opioid tolerance have focused on adaptive modifications within cells containing opioid receptors, defined here as cellular allostasis, emphasizing regulation of the opioid receptor signalosome. We review additional regulatory and opponent processes involved in behavioral tolerance, and include mechanisti...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2016.08.002
更新日期:2016-11-01 00:00:00
abstract::Pharmacology as a modern science was introduced in China approximately 150 years ago, and has been used since then to study traditional Chinese medicine (TCM). Pharmacology has experienced its own development over this time and continues to provide new tools for the study of TCM. In the present review, three models fo...
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::14-3-3 Proteins enact a range of cellular functions through protein-protein interactions (PPIs) with client proteins. Kaplan and colleagues recently demonstrated that a semisynthetic compound was able to selectively stabilize or disrupt specific interactions, depending on the binding partner. This finding presents an ...
journal_title:Trends in pharmacological sciences
pub_type: 评论,杂志文章
doi:10.1016/j.tips.2020.05.001
更新日期:2020-07-01 00:00:00
abstract::Exposure of cells to agonists of receptors linked to G proteins can result in downregulation of cellular levels or redistribution of G proteins from membranes to the cytosol. Agonist-induced reductions in G protein levels have been observed for members of each of the Gs, Gi and Gq families of G proteins, are likely to...
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,评审
doi:10.1016/s0165-6147(99)01406-6
更新日期:1999-12-01 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::This year marks the 90th anniversary of the publication of Hans Horst Meyer's classic paper in which he proposed that the ability of a substance to produce narcosis or anesthesia is governed by its partition coefficient. In this article, Robert Lipnick describes the experiments carried out by Meyer and his colleagues ...
journal_title:Trends in pharmacological sciences
pub_type: 传,历史文章,杂志文章
doi:10.1016/0165-6147(89)90025-4
更新日期:1989-07-01 00:00:00
abstract::Signal transducer and activator of transcription 3 (STAT3) plays crucial roles in several cellular processes such as cell proliferation and survival, and has been found to be aberrantly activated in many cancers. Much research has explored the leading mechanisms for regulating the STAT3 pathway and its role in promoti...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2015.10.001
更新日期:2016-01-01 00:00:00
abstract::Protein kinase Calpha (PKCalpha) is a member of the AGC (which includes PKD, PKG and PKC) family of serine/threonine protein kinases that is widely expressed in mammalian tissues. It is closely related in structure, function and regulation to other members of the protein kinase C family, but has specific functions wit...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2009.10.006
更新日期:2010-01-01 00:00:00
abstract::During the past decade, translocator protein 18 kDa (TSPO), previously named peripheral benzodiazepine receptor, has gained a great deal of attention based on its use as a clinical biomarker of neuroinflammation with therapeutic potential. However, there is a paucity of knowledge on the function(s) of TSPO in glial ce...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2016.02.008
更新日期:2016-05-01 00:00:00
abstract::Insect nicotinic acetylcholine (nACh) receptors are molecular targets of insecticides such as neonicotinoids that are used to control disease-carrying insects and agricultural pests. To date, several insect nACh receptor subunits have been identified, indicating different nACh receptor subtypes and pharmacological pro...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2006.11.006
更新日期:2007-01-01 00:00:00
abstract::Adenosine, when given by inhalation, initiates the narrowing of airways in subjects with asthma or chronic obstructive pulmonary disease (COPD). The underlying mechanism of this narrowing appears to involve the stimulation of specific mast cell surface adenosine receptors with the subsequent release of mediators and c...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
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更新日期:2003-08-01 00:00:00
abstract::Discoidin (DS) domains are found in eukaryotic and prokaryotic extracellular and transmembrane multidomain proteins. These small domains play different functional roles and can interact with phospholipids, glycans, and proteins, including collagens. DS domain-containing proteins are often involved in cellular adhesion...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2016.06.003
更新日期:2016-08-01 00:00:00
abstract::The sialic-acid-binding immunoglobulin-like lectins (siglecs) comprise a family of receptors that are differentially expressed on leukocytes and other immune cells. The restricted expression of several siglecs to one or a few cell types makes them attractive targets for cell-directed therapies. The anti-CD33 (also kno...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2009.02.005
更新日期:2009-05-01 00:00:00
abstract::Chronic obstructive pulmonary disease (COPD) is a pulmonary inflammatory disease that is caused by cigarette smoke. The main characteristic of COPD is the continued inflammation caused by the sustained influx of macrophages and neutrophils into the lung. Recent studies have shed light on how these cells are attracted ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2006.09.003
更新日期:2006-11-01 00:00:00
abstract::The rigorous estimation of a dissociation constant (Kb) for antagonists in functional assays has been sought by pharmacologists using a variety of techniques ever since the regression method of Arunlakshana and Schild in 1959. Here, Michael Lew and James Angus describe a simplified global regression method with improv...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(00)89066-5
更新日期:1995-10-01 00:00:00