Abstract:
:Lou Gehrig's disease, a synonym of amyotrophic lateral sclerosis, is an adult-onset lethal neurodegenerative disorder. Irrespective of extensive efforts to elucidate the pathogenesis of the disease and searches for therapies, no favorable pharmacotherapeutic strategies have yet to be proposed. In a popular rodent model of ALS, G93A SOD1 strain of mouse, intracellular copper conditions were geared toward copper accumulation inside cells, resulting in an acceleration of oxidative stress and apoptotic process. Disruption of intracellular copper homeostasis was common to transgenic mice expressing human mutant SOD1s. In this review, the novel hypothesis that disruption of intracellular copper homeostasis could be involved in the development of the disease was introduced. Based upon the hypothesis, therapeutic outcomes of agents that are capable of correcting and/or modifying intracellular copper homeostasis are described. Administration of ammonium tetrathiomolybdate, a selective intracellular copper chelator, delayed onset, slowed progression, and prolonged survival of a rodent model of the disease (G93A SOD1 mice). Metallothionein is a low molecular weight, cysteine-rich, metal-binding cytoplasmic protein that has beneficial properties in detoxification of toxic heavy metals, homeostatic regulation of intracellular essential trace elements, including copper, antioxidant, and antiapoptotic roles. In animal experiments of the G93A SOD1 mice, an increase of metallothionein proteins by means of induction by exercise or dexamethasone, genetic overexpression, or intraperitoneal administration, all resulted in a preferable outcome. The therapeutic effects were not inferior to those of approved drugs for ALS in humans. These observations suggest that metallothionein could be worth investigating the therapeutic potential in clinical use.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Ono SIdoi
10.2174/1381612823666170622105513subject
Has Abstractpub_date
2017-01-01 00:00:00pages
5001-5009issue
33eissn
1381-6128issn
1873-4286pii
CPD-EPUB-84340journal_volume
23pub_type
杂志文章,评审abstract::Opioid peptides showing selectivity for delta receptor have been isolated from enzymatic digests of plant proteins. Five peptides were derived from wheat gluten, and named gluten exorphins A5, A4, B5, B4 and C. Two opioid peptides were also released from spinach ribulose-bisphosphate-carboxylase/oxygenase (Rubisco), a...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033454838
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:The development of appropriate pharmaceutical formulations for routine neonatal practice is challenging because of the developmental characteristics and the need for it to be specifically ageappropriate. This has led to wide use of extemporaneous formulations, which lack standardized procedures that can resu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170926122613
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Primary aldosteronism is the most common causes of secondary hypertension. Patients suffering from this clinical syndrome have an increased cardiovascular risk and target organ damage. Mineralocorticoid receptor antagonists are the optimal pharmaceutical option for the management of such patients. OBJECTIVE...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190311130138
更新日期:2018-01-01 00:00:00
abstract::The so-called hygiene hypothesis is, at least in part, accountable for the increase in allergic diseases in the developed countries. Although there is support for one of its primary predictions that host-microbe interactions in early life have longterm effects on the development of disease across populations, the theo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212800166031
更新日期:2012-01-01 00:00:00
abstract::The need to identify and characterize vulnerable atherosclerotic lesions in humans has lead to the development of various animal models of plaque vulnerability. In this review, current concepts of the vulnerable plaque as it leads to an acute coronary event are described, such as plaque rupture, erosion, intraplaque h...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207780487575
更新日期:2007-01-01 00:00:00
abstract::Interest in opioid drugs like morphine, as the oldest and most potent pain-killing agents known, has been maintained through the years. One of the most frequent chronic pain sensations people experience is associated with pathological conditions of the musculoskeletal system. Chronic musculoskeletal pain is a major he...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990363
更新日期:2013-01-01 00:00:00
abstract::The so-called demographic transition has changed the age structure of the population worldwide, with profound effects on societal organization. The growing number and percentage of old and very old people has compelled the scientific community to focus on age related diseases and peculiar consequences of aging itself ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777947533
更新日期:2006-01-01 00:00:00
abstract::Aspirin is an antiplatelet drug, inhibiting the cyclooxygenase activity of platelet prostaglandin H synthase-1 and almost complete suppressing platelet capacity to generate the prothrombotic and proatherogenic thromboxane A2. Antiplatelet therapy with aspirin reduces the risk of serious vascular events by about a quar...
journal_title:Current pharmaceutical design
pub_type: 历史文章,杂志文章,评审
doi:10.2174/138161212803251943
更新日期:2012-01-01 00:00:00
abstract::Chronic smoking is associated with functional and structural vascular changes underlying inflammatory processes responsible for plaque formation and rupture. Cyclooxygenase (COX) is the key enzyme linking smoking action to inflammatory damages: it is responsible for the conversion of arachidonic acid to prostanoids, a...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210792062902
更新日期:2010-01-01 00:00:00
abstract::Although acute renal graft rejection rate has declined in the last years, and because an adequate therapy can improve graft outcome, its therapy remains as one of the most significant challenges for pharmacists and physicians taking care of transplant patients. Due to the lack of evidence highlighted by the available ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200610184433
更新日期:2020-01-01 00:00:00
abstract::The complete DNA sequence of the human genome and of several related mammals are now available, due to the investments of enormous resources and advances in sequencing technology. Novel technologies have been developed to compare multiple genomes with each other, thus specifying regions of sequence similarity among ma...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206778559795
更新日期:2006-01-01 00:00:00
abstract::Commonly, the angiogenic growth factors signify healing. However, gastrointestinal ulceration is still poorly understood particularly with respect to a general pharmacological/pathophysiological role of various angiogenic growth factors implemented in growth factors wound healing concept. Thereby, we focused on the st...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180712110447
更新日期:2018-01-01 00:00:00
abstract::Since ancient times the operation of the brain has elicited more than usual interest. Data mining of the human genome is revealing that many CNS abnormalities have a genetic component. As yet this information can not be used directly to cure or ameliorate specific CNS disorders although this is regarded as having grea...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023394250
更新日期:2002-01-01 00:00:00
abstract::Current antiretroviral therapy has had a significant impact on HIV associated morbidity and mortality. Despite these positive outcomes current antiretroviral regimens have significant deficiencies which include multiple drug-drug interactions, high pill burdens, and considerable financial expense. Perhaps the greatest...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206776055868
更新日期:2006-01-01 00:00:00
abstract::P2Y12 adenosine di-phosphate (ADP) receptor antagonists are critical to reduce thrombotic recurrences in acute coronary syndromes patients and for those undergoing percutaneous coronary revascularization. Multiple lines of evidence suggest that the level of on-treatment platelet reactivity inhibition with P2Y12 ADP re...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212803251934
更新日期:2012-01-01 00:00:00
abstract::In the last two decades a tremendous development has been noticed in our understanding of the purinergic system, consisting of heterogeneously expressed purinoceptor subtypes and its classical agonists: e.g., adenosine triphosphate, uridine triphosphate or complex dinucleoside polyphosphates. These agonists exert mult...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212803582504
更新日期:2012-01-01 00:00:00
abstract::All common contributing factors to epilepsy such as trauma, malignancies and infections are accompanied by different levels of central nervous system inflammation that in turn have been associated with the occurrence of seizure. Emerging data from human brain tissue and experimental models of epilepsy support the prop...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319380009
更新日期:2013-01-01 00:00:00
abstract::In this review, the antimicrobial properties of a number of peptides are described. We first deal with helical linear peptides such as the well-known gramicidin, magainins, melittin, and other less well-known or more recently discovered peptides. Then, beta-sheet peptides (defensins isolated from insects and also from...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210793292500
更新日期:2010-01-01 00:00:00
abstract::We set up two models of gastric bleeding in rats using low-dose aspirin (ASA) and the antiplatelet drug clopidogrel, a P2Y₁₂ receptor antagonist, and examined the effect of antiulcer drugs on gastric bleeding and ulcerogenic responses under such conditions. Under urethane anesthesia, two catheters were inserted into t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990418
更新日期:2014-01-01 00:00:00
abstract::While it is well documented that the mitogenic actions of estrogens are critical in the development and progression of human breast and some gynecologic cancers, only latest data demonstrate a crucial involvement of estrogen-signaling in the carcinogenesis of non-classical estrogen target tissues, as colon, prostate, ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212800626139
更新日期:2012-01-01 00:00:00
abstract::The term endozepines designates a family of astroglia-secreted proteins including the diazepambinding inhibitor (DBI) and its processing products, which have been originally isolated and characterized as endogenous ligands of benzodiazepine receptors. It is now clearly established that the octadecaneuropeptide ODN (DB...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666181112111746
更新日期:2018-01-01 00:00:00
abstract::Inhibition of the renin-angiotensin system (RAS) has been shown to have beneficial effects in cardiovascular disease prognosis and therapy.Discovery of (pro)renin receptor [(P)RR] revealed that (P)RR upon binding to both renin or prorenin in their proenzyme inactive form made them enzymatically active, thus aiding the...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990472
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Discovery and development of BCS class 1 drugs through high throughput screening is one of the biggest challenge faced by formulation scientist. METHODS:There are a number of approaches that have been exploited to enhance the solubility and permeability of drugs. Among them, development of nanosuspension ha...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180522100251
更新日期:2018-01-01 00:00:00
abstract::Cardiovascular diseases remain the leading cause of morbidity and mortality among postmenopausal women in western societies. There are still no specific and highly efficient methods of preservation of women's vascular health in modern preventive medicine. For many years physicians have assumed that hormone replacement...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151112150520
更新日期:2016-01-01 00:00:00
abstract::Natural products, or their synthetic derivatives are a treasure trove to find potential candidates for novel drugs for human treatment. The selection of diamonds from the huge pile of worthless stone is a critical--and difficult--stage in the discovery pipeline. Of all the factors to be considered, perhaps the most im...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666151002114227
更新日期:2015-01-01 00:00:00
abstract::In the classical renin angiotensin system (RAS), angiotensin II Ang IIplays many important roles in cardiovascular disease and in kidney, brain, and other organs via the Ang II type 1 receptor (AT1). The RAS consists of many angiotensin peptides, including Ang (1-7), Ang (1-9), Ang (2-8), and Ang IV. Ang (1-7), produc...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319170013
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:On a tide of big data, machine learning is coming to its day. Referring to huge amounts of epigenetic data coming from biological experiments and clinic, machine learning can help in detecting epigenetic features in genome, finding correlations between phenotypes and modifications in histone or genes, accele...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666181112114228
更新日期:2018-01-01 00:00:00
abstract::The OB-receptor or leptin receptor (LR) is crucial for energy homeostasis and regulation of food uptake. Leptin is a 16 kDa hormone that is mainly secreted by fat cells into the bloodstream. Under normal circumstances, circulating leptin levels are proportionate to the fat body mass. Sensing of elevated leptin levels ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113196660743
更新日期:2014-01-01 00:00:00
abstract::A severe atypical pneumonia designated as severe acute respiratory syndrome (SARS) by The World Health Organization broke out in China and menaced to more than other 30 countries between the end of the year 2002 and June of the year 2003. A novel coronavirus called severe acute respiratory syndrome coronavirus (SARS-C...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206779010459
更新日期:2006-01-01 00:00:00
abstract::Tumor necrosis factor alpha (TNF-α) is a multi-functional cytokine that regulates a variety of signaling pathways implicated in inflammation, immunity, cell death (apoptosis), cell survival (anti-apoptosis), and even tumorigenesis. TNF-α is predominantly produced by macrophages (or Kupffer cells within the liver), but...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990587
更新日期:2014-01-01 00:00:00