Abstract:
:It is well documented that elevated levels of PAI-1 in plasma can decrease the fibrinolytic activity in blood with an associated increased risk of thrombus formation. A diverse range of molecules including bacterial lipopolysaccharide (LPS), the inflammatory mediators tumor necrosis factor alpha (TNFalpha) and interleukins, thrombin, transforming growth factor-beta (TGF-beta), and hormones regulate the synthesis of plasma PAI-1. Therefore, it is of clinical importance to restore the fibrinolytic balance. For a drug to be effective in controlling the synthesis of PAI-1, sufficient insight into the signal transduction pathways that control its regulation is desirable, which could serve as logical targets for the development of pharmaceuticals. Some key signaling pathways have been identified with the aid of pharmacological inhibitors, involved in the up-regulation of PAI-1 in context with several diseases, including obesity, insulin resistance, diabetic nephropathy, glomulonephritis, and pulmonary fibrosis. Furthermore, independent of its inhibitory activity PAI-1 mediates interactions with vitronectin (VN) and low density lipoprotein receptor-related protein (LRP) which modifies basic cell behaviors of proliferation, migration, and attachment. Intriguingly, it has been shown that both anti-fibrinolytic and non-fibrinolytic-related functions of PAI-1 may have overlapping roles in many diseases that are poorly understood. Tailoring knock-in mice with site-specific alterations that diminish the inhibitory activity, VN-binding, and LRP-binding activity of PAI-1 are useful tools for manipulation of biochemical properties, in vivo, and evaluating therapeutics.
journal_name
Curr Drug Targetsjournal_title
Current drug targetsauthors
Balsara RD,Xu Z,Ploplis VAdoi
10.2174/138945007781662382subject
Has Abstractpub_date
2007-09-01 00:00:00pages
982-95issue
9eissn
1389-4501issn
1873-5592journal_volume
8pub_type
杂志文章,评审abstract:BACKGROUND:The mitochondria may very well determine the final commitment of the cell to death, particularly in times of energy stress. Cancer chemotherapeutics such as the anthracycline doxorubicin perturb mitochondrial structure and function in tumour cells, as evidenced in osteosarcoma, for which doxorubicin is used ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450116666150416115852
更新日期:2018-01-01 00:00:00
abstract::Currently, low density lipoprotein cholesterol (LDL-C) levels are the main, if not the only, lipid target in the effort to reduce cardiovascular disease (CVD) morbidity and mortality. Several primary and secondary CVD prevention trials with statins shaped current guidelines and provided detailed targets across a range...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945007780058933
更新日期:2007-03-01 00:00:00
abstract:BACKGROUND:Alzheimer's disease, a neurodegenerative disorder, is characterized by accumulation of amyloid beta (Aβ) plaques, neurofibrillary tangles and loss of cholinergic neurons. LITERATURE REVIEW:The localization of Aβ plaques particularly in the cholinergic neuron-rich areas has led to the discovery that Aβ binds...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666161005145143
更新日期:2017-01-01 00:00:00
abstract::One approach to identify new drugs with antimicrobial activities is to screen large libraries of molecules directly for their capacity to block the growth of bacterial or fungal monocultures. A more relevant way to assess both a product's efficacy and its potential cytotoxicity is undoubtedly to use an in vivo infecti...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945011795677854
更新日期:2011-06-01 00:00:00
abstract::Seventy five percent of hospitalized patients with Crohn's disease suffer from malnutrition. One third of Crohn's disease patients have a body mass index below 20. Sixty percent of Crohn's disease patients have sarcopenia. However some inflammatory bowel disease (IBD) patients are obese or suffer from sarcopenic-obesi...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450115666140930150047
更新日期:2014-01-01 00:00:00
abstract::Multidrug resistance (MDR) is a kind of acquired resistance of microorganisms and cancer cells to chemotherapic drugs that are characterized by different chemical structure and different mechanism of action. Classic MDR is the consequence of the over-expression of a variety of proteins that extrude the chemotherapic f...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945006777709520
更新日期:2006-07-01 00:00:00
abstract::Recently, the presence of functional interaction between the opioid and cannabinoid system has been shown in various pharmacological responses. Although there is an increasing interest for the feasible therapeutic application of a co-administration of cannabinoids and opioids in some disorders (i.e. to manage pain, to...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945010790980367
更新日期:2010-04-01 00:00:00
abstract::Medical chronobiology deals with the way body's rhythm influences a person's health and disease states. To match body rhythms, deliberate alteration of drug concentration is done to optimize therapeutic outcomes and minimize size effects and this approach is known as Chronotherapeutics. In general the concept of homeo...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450120666190527114529
更新日期:2019-01-01 00:00:00
abstract::Epidemiological studies provide a growing number of evidences that chronic exposure to relatively low levels of cadmium (Cd), nowadays taking place in industrialized countries, may cause health hazard. Thus, growing interest has been focused on effective ways of protection from adverse effects of exposure to this heav...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450116666150506114336
更新日期:2016-01-01 00:00:00
abstract::Trypanosomes and Leishmaniae are the agents of several important parasitic diseases threatening hundreds of million human beings worldwide. As they diverged early in evolution, they display original molecular characteristics. These peculiarities are each defining putative specific targets for anti-parasitic drugs. Tra...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945008786786064
更新日期:2008-11-01 00:00:00
abstract::Vascular Disrupting Agents (VDA) are a potential new class of oncology drugs that have garnered attention recently as a number of these agents have entered into Phase 2-3 studies. Currently available data suggest how the subsequent evolution of these agents into clinical practice may proceed, with new therapeutic para...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945011798829366
更新日期:2011-12-01 00:00:00
abstract::The growing number of cellular and molecular pathways believed to be involved in mechanisms of ischemic cell death in the brain has spurred a similar growth in the number of potential neuroprotective modalities, the majority of which are pharmacological in nature. Preventing or minimizing the first few steps in the ca...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450043345209
更新日期:2004-10-01 00:00:00
abstract::Nature provides science and society with a virtually unlimited supply of structurally diverse and biologically active molecules; the natural products. While some are directly useful in commercial applications, others are valuable for studying and understanding biological phenomena at the molecular level. An example is...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945011798109509
更新日期:2011-10-01 00:00:00
abstract::Heme oxygenase-1 (HO-1) metabolizes heme to generate carbon monoxide (CO), biliverdin, and iron. Biliverdin is subsequently metabolized to bilirubin by biliverdin reductase. HO-1 has recently emerged as a promising therapeutic target in the treatment of vascular disease. Pharmacological induction or gene transfer of H...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450111009011504
更新日期:2010-12-01 00:00:00
abstract::Immunity is a balanced status with adequate biological defenses to recognize and fight "non-self", as well as adequate tolerance to recognize "self". To maintain this immune homeostasis, a well-organized T cell immune network is required, which in part depends on the well-controlled development of alternative effector...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666161124145641
更新日期:2017-01-01 00:00:00
abstract::To initiate the innate immune response, Toll-like receptors (TLRs) associate with cytoplasmic adaptor proteins through TIR (Toll/interleukin-1 receptor) domain interactions. The four principal signaling adaptor proteins include MyD88, MAL, TRIF and TRAM, and the fifth protein SARM, involved in negative regulation of T...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945012803530260
更新日期:2012-10-01 00:00:00
abstract::Hepatitis C virus (HCV), a member of the Flaviviridae family, has been recognised to be responsible for both parenterally transmitted and sporadic non-A and non-B hepatitis affecting 1-3% of the world population. HCV is a positive stranded RNA virus encoding a single polyprotein which contains at least ten unique stru...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450023347650
更新日期:2002-08-01 00:00:00
abstract::Prostate cancer is the most common and second most lethal cancer in men. The majority of prostate cancers are histologically similar to acinar adenocarcinomas and rely on androgen-dependent signaling for their development and progression. Androgen deprivation therapy is a mainstay of treatment regimens and we discuss ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450115666141229154500
更新日期:2015-01-01 00:00:00
abstract::Antimicrobial resistance of human pathogenic bacteria is an emerging problem for global public health. This resistance is often associated with the overproduction of membrane transport proteins that are capable to pump chemotherapeutics, antibiotics, detergents, dyes and organic solvents out of the cell. In Gram-negat...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945008785747789
更新日期:2008-09-01 00:00:00
abstract::A group of oxytocinergic neurons originating in the paraventricular nucleus of the hypothalamus and projecting to extrahypothalamic brain areas (e.g. hippocampus, medulla oblongata and spinal cord) control penile erection. Activation of these neurons by dopamine and dopamine agonists, excitatory amino acids (N-methyl-...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450033347190
更新日期:2003-01-01 00:00:00
abstract::As early as 1940, Abraham and Chain described "an enzyme able to destroy penicillin". In the late 1940's, penicillin-resistant strains of Staphylococcus aureus were found to be a clinical problem. They produced a penicillinase that could hydrolyze the amide bond in the β-lactam ring. Later, an enzyme mediated by an R-...
journal_title:Current drug targets
pub_type: 历史文章,杂志文章,评审
doi:10.2174/1389450116666151001112859
更新日期:2016-01-01 00:00:00
abstract::Anticancer peptide (ACP) is a kind of small peptides that can kill cancer cells without damaging normal cells. In recent years, ACP has been pre-clinically used for cancer treatment. Therefore, accurate identification of ACPs will promote their clinical applications. In contrast to labor-intensive experimental techniq...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450119666180801121548
更新日期:2019-01-01 00:00:00
abstract::Fracture healing is a process of recovering injured bone tissue forms and functions. Osteoporosis can delay the healing process, which contributes to personal suffering and loss of activities. Osteoporosis patients tend to lose bone mass at the metaphyseal region which require treatment to increase bone mass. Postmeno...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/13894501113149990195
更新日期:2013-12-01 00:00:00
abstract::Overexpression of the human epidermal growth factor receptor 2 (HER2) is identified in approximately 25- 30% of breast cancers and indicates a poor prognosis. Trastuzumab, the anti-HER2 monoclonal antibody (mAb), has shown significant clinical effects selectively in HER2-overexpressing metastatic breast cancer (MBC) w...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/13894501113149990161
更新日期:2013-07-01 00:00:00
abstract::Adipose tissue plays an active role in energy balance because it is not only a lipid storing and mobilizing tissue but consists of functionally specialized tissues able to produce heat (in brown adipose tissue) and to produce or release a vast number of so called adipokines or adipocytokines. These consist of polypept...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450043490523
更新日期:2004-04-01 00:00:00
abstract::Antiphospholipid syndrome (APS) is characterized by a combination of clinical features consisted of thrombotic or pregnancy-related events and autoimmune antiphospholipid antibodies. In the 1998 International Consensus Preliminary Criteria, APS is defined by the concomitant presence of these clinical features and labo...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450054545999
更新日期:2005-08-01 00:00:00
abstract::Enzymes are proteins that act as biological catalysts to speed up cellular biochemical processes. According to their main Enzyme Commission (EC) numbers, enzymes are divided into six categories: EC-1: oxidoreductase; EC-2: transferase; EC-3: hydrolase; EC-4: lyase; EC-5: isomerase and EC-6: synthetase. Different enzym...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450119666181002143355
更新日期:2019-01-01 00:00:00
abstract::Histone deacetylases are a class of enzymes that play important roles in post translational modifications of histones by deacetylating the lysine residues as well as interacting with various non-histone proteins. This type of enzymes is closely related to oncogenesis and has been proved to be attractive targets for de...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450115666140306152642
更新日期:2014-06-01 00:00:00
abstract::Crohn's disease (CD) and ulcerative colitis (UC), two chronic and relapsing inflammatory bowel diseases (IBD), are supposed to develop in genetically-predisposed individuals as a result of an excessive immune mucosal response directed against normal components of the gut microbiota. There is also evidence that defects...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/13894501113149990157
更新日期:2013-11-01 00:00:00
abstract::At one time, atherosclerosis was thought to be a simple lipid storage disease. However, it is now recognized as a chronic and progressive inflammation of the arterial wall. Gene deletion experiments in murine models of atherosclerosis that reduce the inflammatory process also reduce disease severity. Identifying the i...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945007783220605
更新日期:2007-12-01 00:00:00