Abstract：
:Cyclooxygenase (COX) enzymes, or prostaglandin-endoperoxide synthases (PTGS), are heme-containing bis-oxygenases that catalyze the first committed reaction in metabolism of arachidonic acid (AA) to the potent lipid mediators, prostanoids and thromboxanes. Two isozymes of COX enzymes (COX-1 and COX-2) have been identified to date. This review will focus specifically on the neurobiological and neuropathological consequences of AA metabolism via the COX-2 pathway and discuss the potential therapeutic benefit of COX-2 inhibition in the setting of neurological disease. However, given the controversy surrounding the use of COX-2 selective inhibitors with respect to cardiovascular health, it will be important to move beyond COX to identify which down-stream effectors are responsible for the deleterious and/or potentially protective effects of COX-2 activation in the setting of neurological disease. Important advances toward this goal are highlighted herein. Identification of unique effectors in AA metabolism could direct the development of new therapeutics holding significant promise for the prevention and treatment of neurological disorders.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Hewett SJ,Bell SC,Hewett JAdoi
10.1016/j.pharmthera.2005.04.011subject
Has Abstractpub_date
2006-11-01 00:00:00pages
335-57issue
2eissn
0163-7258issn
1879-016Xpii
S0163-7258(06)00064-7journal_volume
112pub_type
杂志文章,评审abstract：:This review provides biochemical, analytical, and biological background information relating to beta-N-acetylhexosaminidase (HexNAc'ase; EC 3.2.1.52) as an emerging target for the design of low-molecular-weight antifungals. The article includes the following: (1) a biochemical description of HexNAc'ase (reaction catal...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(97)00110-1
更新日期：1997-10-01 00:00:00
abstract：:There is substantial molecular evidence for the involvement of beta1 integrin in tissue organisation and remodelling, which confers a key role in cell growth, differentiation, migration, and survival. This role has been, in part, highlighted using the transgenic approach which does little to define the more subtle fun...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2008.07.002
更新日期：2008-11-01 00:00:00
abstract：:Dipeptidyl peptidase 4 (DPP4, DPPIV, CD26, EC 3.4.14.5) was discovered more than four decades ago as a serine protease that cleaves off N-terminal dipeptides from peptide substrates. The development of potent DPP4 inhibitors during the past two decades has led to the identification of DPP4 as a target in the treatment...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.07.012
更新日期：2012-12-01 00:00:00
abstract：:Aspirin is integral to the secondary prevention of cardiovascular disease and acts to impair the development of platelet-mediated atherothromboembolic events by irreversible inhibition of platelet cyclooxygenase-1 (COX-1). Inhibition of this enzyme prevents the synthesis of the potent pro-aggregatory prostanoid thromb...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2013.08.005
更新日期：2014-01-01 00:00:00
abstract：:The importance of regular administration of antiplatelet drugs in patients suffering from coronary artery disease stands on firm grounds, as large meta-analyses have shown these therapies to drastically reduce the risk of death. Although the current guidelines published jointly by the American Heart Association, the A...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2009.03.019
更新日期：2009-08-01 00:00:00
abstract：:Artemisinins are a unique class of antimalarial drugs with significant potential for drug repurposing for a wide range of diseases including cancer. Cancer is a leading cause of death globally and the majority of cancer related deaths occur in Low and Middle Income Countries (LMICs) where conventional treatment option...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107706
更新日期：2020-12-01 00:00:00
abstract：:5-Lipoxygenase (5-LO) catalyzes the conversion of arachidonic acid (AA) into leukotriene (LT) A(4) and 5-hydroperoxyeicosatetraenoic acid. LTA(4) can then be converted into LTB(4) by LTA(4) hydrolase or into LTC(4) by LTC(4) synthase and the LTC(4) synthase isoenzymes MGST2 and MGST3. LTB(4) is a potent chemoattractan...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2006.05.009
更新日期：2006-12-01 00:00:00
abstract：:Minor groove binders are small molecules that form strong complexes with the minor groove of DNA. There are several structural types of which distamycin and netropsin analogues, oligoamides built from heterocyclic and aromatic amino acids, and bis-amidines separated by aromatic and heterocyclic rings are of particular...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2013.03.002
更新日期：2013-07-01 00:00:00
abstract：:Myocarditis is a heterogeneous group of disorders defined by inflammation of the heart muscle. The primary clinical manifestations of myocarditis are heart failure and sudden death in children and young adults. Numerous interventions have been investigated for the treatment of myocarditis, including broad spectrum alt...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.03.006
更新日期：2016-05-01 00:00:00
abstract：:Thoracic aortic aneurysms (TAAs) are a potential life-threatening disease with limited pharmacological treatment options. Current treatment options are aimed at lowering aortic hemodynamic stress, predominantly with β-adrenoceptor blockers. Increasing evidence supports a role for the renin-angiotensin system (RAS) in ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.04.002
更新日期：2011-07-01 00:00:00
abstract：:A number of inherited or drug-induced metabolic disorders involving dysfunctions in purines and pyrimidines are strongly associated with neurological dysfunction, e.g., Lesch Nyhan syndrome. Such disorders have been studied extensively using biochemical and molecular techniques in order to examine how such defects occ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(01)00141-3
更新日期：2001-05-01 00:00:00
abstract：:High-mobility group box 1 (HMGB1) is one of the most abundant proteins in eukaryotes and the best characterized damage-associated molecular pattern (DAMP). The biological activities of HMGB1 depend on its subcellular location, context and post-translational modifications. Inside the nucleus, HMGB1 is engaged in many D...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.12.005
更新日期：2019-04-01 00:00:00
abstract：:The demonstration that RNA can be cleaved by cis or trans ribozymes (catalytic RNAs, RNA enzymes) has potentially important therapeutic implications. Since their discovery in the 1980s, the biochemistry and conserved sequences of ribozymes have been well characterized. Ribozymes are effective modulators of gene expres...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(95)02008-x
更新日期：1995-01-01 00:00:00
abstract：:Granulocytes are defined as the population of granulated white blood cells (eosinophils, neutrophils, and basophils). These cells are involved in inflammation and contribute to the pathogenesis of allergic and inflammatory diseases. Inflammation is induced by the release of mediators from granulocytes recruited to or ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.03.008
更新日期：2005-09-01 00:00:00
abstract：:Mammals dispose of cholesterol mainly through 7alpha-hydroxylated bile acids, and the enzyme catalyzing the 7alpha-hydroxylation, cholesterol 7alpha-hydroxylase (CYP7A1), has a deep impact on cholesterol homeostasis. In this review, we present the study of regulation of CYP7A1 as a good exemplification of the extraord...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2007.08.003
更新日期：2007-12-01 00:00:00
abstract：:The use of Translocator Protein 18 kDa (TSPO) as a clinical neuroimaging biomarker of brain injury and neuroinflammation has increased exponentially in the last decade. There has been a furious pace in the development of new radiotracers for TSPO positron emission tomography (PET) imaging and its use has now been exte...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.09.003
更新日期：2019-02-01 00:00:00
abstract：:The 90-kDa molecular chaperone family (which comprises, among other proteins, the 90-kDa heat-shock protein, hsp90 and the 94-kDa glucose-regulated protein, grp94, major molecular chaperones of the cytosol and of the endoplasmic reticulum, respectively) has become an increasingly active subject of research in the past...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(98)00013-8
更新日期：1998-08-01 00:00:00
abstract：:Nitric oxide (NO) exerts a variety of biological actions under both physiological and pathological conditions. NO is synthesized by three distinct NO synthase (NOS) isoforms, including neuronal (nNOS), inducible (iNOS), and endothelial NOS (eNOS), all of which are expressed in the human cardiovascular system. The role...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2010.08.010
更新日期：2010-12-01 00:00:00
abstract：:QT interval prolongation, corrected for heart rate (QTc), either spontaneous or drug-induced, is associated with an increased risk of torsades de pointes and sudden death. Women have longer QTc than men and are at higher risk of torsades de pointes, particularly during post-partum and the follicular phase. Men with pe...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.07.005
更新日期：2016-11-01 00:00:00
abstract：:Synaptic inhibition plays a key role in regulating neuronal excitability and information processing in the brain. The strength of synaptic inhibition is therefore an important determinant of both cellular and network activity levels in the central nervous system (CNS). gamma-aminobutyric acid type A (GABA(A)) receptor...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章
doi：10.1016/j.pharmthera.2009.03.012
更新日期：2009-07-01 00:00:00
abstract：:Considering both cancer's serious impact on public health and the side effects of cancer treatments, strategies towards targeted cancer therapy have lately gained considerable interest. Employment of gold nanoparticles (GNPs), in combination with ionizing and non-ionizing radiations, has been shown to improve the effe...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2017.03.006
更新日期：2017-10-01 00:00:00
abstract：:Exacerbations of asthma are the main cause of asthma morbidity. They induce acute respiratory failure, and sometimes death. Two immunological signals acting in synergy are necessary for inducing asthma exacerbations. The first, triggered by allergens and/or unknown agents leads to the chronic Th2 inflammation characte...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.03.010
更新日期：2011-07-01 00:00:00
abstract：:Polycyclic aromatic hydrocarbons (PAH) are carcinogens requiring metabolic activation to react with cellular macromolecules, the initial event in carcinogenesis. Cytochrome P450 mediates binding of PAH to DNA by two pathways of activation. One-electron oxidation to form radical cations is the major pathway of activati...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(92)90015-r
更新日期：1992-01-01 00:00:00
abstract：:The understanding of renal fibrosis in chronic kidney disease (CKD) remains as a challenge. More than 10% of the population of developed countries suffer from CKD. Proliferation and activation of myofibroblasts and accumulation of extracellular matrix proteins are the main features of kidney fibrosis, a process in whi...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2015.10.003
更新日期：2015-12-01 00:00:00
abstract：:Patients of congenital diseases such as Down syndrome (DS) and Duchenne muscular dystrophy (DMD) have abnormalities in their chromosomes and/or genes. Therefore, it has been considered that drug treatments can serve to do little for these patients more than to patch over each symptom temporarily when it arises. Althou...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.02.001
更新日期：2012-06-01 00:00:00
abstract：:Chemoresistant metastatic relapse of minimal residual disease plays a significant role for poor prognosis of cancer. Growing evidence supports a critical role of cancer stem cell (CSC) behind the mechanisms for this deadly disease. This review briefly introduces the basics of the conventional chemotherapies, updates t...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.02.008
更新日期：2016-04-01 00:00:00
abstract：:Mechanistic insights of cancer immunology have led to the development of immune checkpoint blockade therapy (ICBT), which has elicited a remarkable clinical response in some cancer patients. Increasing evidence suggests that activation of oncogenic pathways, such as RAS/RAF/MAPK and PI3K signaling, impairs the antitum...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2017.07.004
更新日期：2018-01-01 00:00:00
abstract：:Cardiovascular disease (CVD) continues to be a leading cause of death worldwide with atherosclerosis being the major underlying pathology. The interplay between lipids and immune cells is believed to be a driving force in the chronic inflammation of the arterial wall during atherogenesis. Atherosclerosis is initiated ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.08.012
更新日期：2019-01-01 00:00:00
abstract：:While antibiotics revolutionized the treatment of infectious disease in the 20th century, bacterial resistance now threatens to render many of them ineffective. Aminoglycosides are a class of clinically important antibiotics used in the treatment of infections caused by Gram-positive and -negative organisms. They are ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(02)00197-3
更新日期：2002-02-01 00:00:00
abstract：:This article reviews uses of metabolic suicide genes in gene therapy. Suicide genes encode novel nonmammalian enzymes that can convert a relatively nontoxic prodrug into a highly toxic agent. Cells genetically transduced to express such genes essentially commit metabolic suicide in the presence of the appropriate prod...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(94)90046-9
更新日期：1994-08-01 00:00:00
