Abstract:
:Severe and prolonged impairment of mitochondrial beta-oxidation leads to microvesicular steatosis, and, in severe forms, to liver failure, coma and death. Impairment of mitochondrial beta-oxidation may be either genetic or acquired, and different causes may add their effects to inhibit beta-oxidation severely and trigger the syndrome. Drugs and some endogenous compounds can sequester coenzyme A and/or inhibit mitochondrial beta-oxidation enzymes (aspirin, valproic acid, tetracyclines, several 2-arylpropionate anti-inflammatory drugs, amineptine and tianeptine); they may inhibit both mitochondrial beta-oxidation and oxidative phosphorylation (endogenous bile acids, amiodarone, perhexiline and diethylaminoethoxyhexestrol), or they may impair mitochondrial DNA transcription (interferon-alpha), or decrease mitochondrial DNA replication (dideoxynucleoside analogues), while other compounds (ethanol, female sex hormones) act through a combination of different mechanisms. Any investigational molecule should be screened for such effects.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Fromenty B,Pessayre Ddoi
10.1016/0163-7258(95)00012-6subject
Has Abstractpub_date
1995-01-01 00:00:00pages
101-54issue
1eissn
0163-7258issn
1879-016Xpii
0163725895000126journal_volume
67pub_type
杂志文章,评审abstract::Hypoxia inducible factor (HIF) is an oxygen-sensitive transcription factor that enables aerobic organisms to adapt to hypoxia. This is achieved through the transcriptional activation of up to 200 genes, many of which are critical to cell survival. Under conditions of normoxia, the hydroxylation of HIF by prolyl hydrox...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2012.07.005
更新日期:2012-10-01 00:00:00
abstract::Nongenomic estrogen signaling pathways involve extranuclear estrogen receptors or function independently from estrogen receptors. These pathways participate in neuroprotection elicited by the hormone. Additional nongenomic neuroprotective effects are attributable to antioxidant and antiinflammatory actions of estrogen...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2007.01.006
更新日期:2007-04-01 00:00:00
abstract::Arthritis is a chronic disease of joints. It is highly prevalent, particularly in the elderly, and is commonly associated with pain that interferes with quality of life. Because of its chronic nature, pharmacological approaches to pain relief and joint repair must be safe for long term use, a quality many current ther...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2018.02.015
更新日期:2018-07-01 00:00:00
abstract::Evidence that the delta opioid receptor (DOR) is an attractive target for the treatment of brain disorders has strengthened in recent years. This receptor is broadly expressed in the brain, binds endogenous opioid peptides, and shows as functional profile highly distinct from those of mu and kappa opioid receptors. Ou...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2013.06.003
更新日期:2013-10-01 00:00:00
abstract::A variety of drug transporters expressed in the body control the fate of drugs by affecting absorption, distribution, and elimination processes. In the small intestine, transporters mediate the influx and efflux of endogenous or exogenous substances. In clinical pharmacotherapy, ATP-dependent efflux transporters (ATP-...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2005.06.005
更新日期:2006-01-01 00:00:00
abstract::Angiotensin II (Ang II) is the main effector hormone of the renin-angiotensin system (RAS). The pathogenesis of many cardiovascular diseases, including heart failure and hypertension, appear to be related to Ang II production. The generation of Ang II involves angiotensin-converting enzyme (ACE) in circulating and tis...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0163-7258(97)00021-1
更新日期:1997-01-01 00:00:00
abstract::Microsomal P450-mediated monooxygenase activity supported by NADPH requires an interaction between flavoprotein NADPH-cytochrome P450 reductase and cytochrome P450. These proteins have been identified as the simplest system (with the inclusion of a phospholipid (PL) component) that possesses monooxygenase function; ho...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0163-7258(03)00031-7
更新日期:2003-05-01 00:00:00
abstract::RANKL is a key molecule that bridges the bone and immune systems. RANKL stimulation activates a signaling pathway downstream of RANK, thereby determining the extent of bone resorption by inducing osteoclast maturation. The signaling pathway also regulates the development of different lymphoid organs, including the thy...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2020.107682
更新日期:2021-02-01 00:00:00
abstract::The small heat shock proteins (HSPs) HSP20, HSP27 and alphaB-crystallin are chaperone proteins that are abundantly expressed in smooth muscles are important modulators of muscle contraction, cell migration and cell survival. This review focuses on factors regulating expression of small HSPs in smooth muscle, signaling...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2008.04.005
更新日期:2008-07-01 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::S-Adenosylhomocysteine (AdoHcy), formed after the donation of the methyl group of S-adenosylmethionine to a methyl acceptor, is hydrolyzed to adenosine and homocysteine by AdoHcy hydrolase physiologically. The administration of the inhibitors of AdoHcy hydrolase to cells or animals normally results in an accumulation ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0163-7258(97)00089-2
更新日期:1998-02-01 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::Neuropeptides are the largest class of intercellular signaling molecules, contributing to a wide variety of physiological processes. Neuropeptide receptors are therapeutic targets for a broad range of drugs, including medications to treat pain, addiction, sleep disorders, and nausea. In addition to >100 peptides with ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2017.11.006
更新日期:2018-05-01 00:00:00
abstract::The receptor tyrosine kinase MERTK is aberrantly expressed in numerous human malignancies, and is a novel target in cancer therapeutics. Physiologic roles of MERTK include regulation of tissue homeostasis and repair, innate immune control, and platelet aggregation. However, aberrant expression in a wide range of liqui...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2020.107577
更新日期:2020-09-01 00:00:00
abstract::Although potent effects of psychoactive drugs on circadian rhythms were first described over 30 years ago, research into the reciprocal relationship between the reward system and the circadian system - and the impact of this relationship on addiction - has only become a focus in the last decade. Nonetheless, great pro...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2018.03.003
更新日期:2018-08-01 00:00:00
abstract::Biogenic amine transporters for serotonin, norepinephrine and dopamine (SERT, NET and DAT respectively), are the key players terminating transmission of these amines in the central nervous system by their high-affinity uptake. They are also major targets for many antidepressant drugs. Interestingly however, drugs targ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2008.10.004
更新日期:2009-01-01 00:00:00
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::Hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors are a class of lipid-lowering medications, with a major activity on plasma cholesterol levels, now enjoying a vast popularity among physicians and patients. These drugs, affecting a very early and key step of sterol biosynthesis, differ to a large extent ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/0163-7258(93)90031-8
更新日期:1993-12-01 00:00:00
abstract::Relationship between inflammation and cancer is now well-established and represents a paradigm that our immune response does not necessarily serves solely to protect us from infections and cancer. Many specific mechanisms that link chronic inflammation to cancer promotion and metastasis have been uncovered in the rece...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2016.09.011
更新日期:2016-12-01 00:00:00
abstract::Drug therapy directed toward the fetus would be intended for either treating a fetal disorder or improving the capacity for later intrauterine or postnatal adaptation. Most reported trials involve single cases or small numbers of fetuses receiving the drug transplacentally after the first trimester, but before attaini...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/0163-7258(93)90051-e
更新日期:1993-01-01 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::Stroke is a major clinical problem, and acute pharmacological intervention with neuroprotective agents has so far been unsuccessful. Recently, there has been considerable interest in the potential therapeutic benefit of nitrone-derived free radical trapping agents as neuroprotective agents. Nitrone compounds have been...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2003.07.003
更新日期:2003-12-01 00:00:00
abstract::Stroke and myocardial infarction are among the most common causes of mortality and disability in the world. The ischemic injury underlying these illnesses is complex, involving intricate interplays among many biological functions including energy metabolism, vascular regulation, hemodynamics, oxidative stress, inflamm...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2018.05.006
更新日期:2018-10-01 00:00:00
abstract::Sphingolipid metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate (S1P), play many important roles in cellular activities. Ceramide and sphingosine inhibit cell proliferation and induce cell apoptosis while S1P has the opposite effect. Maintaining a metabolic balance of sphingolipids is essential for...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2018.10.011
更新日期:2019-03-01 00:00:00
abstract::This review focuses on the chemical and enzymatic aspects of the reductive activation of mitomycin C, its disulfide analogs KW-2149 and BMS-181174, and, in less detail, FR66979 and FR900482, newly discovered antitumor antibiotics related to mitomycins. Furthermore, structural aspects of DNA damage induced by these dru...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0163-7258(97)00088-0
更新日期:1997-10-01 00:00:00
abstract::The smooth muscle of the normal bladder wall must have some specific properties. It must be very compliant and able to reorganise itself during filling and emptying to accommodate the change in volume without generating any intravesical pressure, but whilst maintaining the normal shape of the bladder. It must be capab...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0163-7258(97)00038-7
更新日期:1997-08-01 00:00:00
abstract::The neurobiological processes by which ethanol seeking and consumption are established and maintained are thought to involve areas of the brain that mediate motivated behavior, such as the mesolimbic dopamine system. The mesolimbic dopamine system is comprised of cells that originate in the ventral tegmental area (VTA...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2004.06.002
更新日期:2004-08-01 00:00:00
abstract::Hybrid polar compounds, of which hexamethylene bisacetamide (HMBA) is the prototype, have been shown to be potent inducers of differentiation of many types of transformed cells. With virus-transformed murine erythroleukemia cells as a model, HMBA was shown to cause these cells to arrest in G1 phase and express globin ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/0163-7258(95)02044-6
更新日期:1996-01-01 00:00:00
abstract::Drug-induced arrhythmias or QT interval prolongation is one of the two most common reasons for drugs to be denied regulatory approval or to have warnings imposed on their clinical labelling. The assessment of torsades de pointes (TdP) risk during clinical development of a new pharmaceutical compound has been an issue ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章
doi:10.1016/j.pharmthera.2008.05.006
更新日期:2008-08-01 00:00:00
abstract::In the search for new approaches to cancer therapy, the first alkyllysophospholipid (ALP) analogs were designed and studied about two decades ago, either as potential immunomodulators or as antimetabolites of phospholipid metabolism. In the meantime, it has been demonstrated that they really act in this way. However, ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/0163-7258(95)00001-w
更新日期:1995-04-01 00:00:00