Abstract:
:Ion channel dysfunction has been identified as a contributor to symptom development and neurodegeneration in multiple sclerosis (MS). The molecular insights have been translated into new lines of research, with ion channel modulation now representing a therapeutic approach in MS. Studies of Na+ channel function have demonstrated pathological blockade of Na(+) channels during an acute inflammatory attack. Relapses are typically associated with subsequent alterations in Na+ channel expression and structure. However, these compensatory changes may also be deleterious. Specifically, increased Na(+) channel expression may contribute to neuronal energy insufficiency and a cascade of events that may ultimately lead to neurodegeneration and apoptosis. Pharmacological blockade of Na(+) channels in animal models of MS demonstrated encouraging results, although mixed results were obtained in subsequent clinical trials in MS patient cohorts. The process involved in demyelination, a characteristic event in MS pathology, may also induce complex structural changes mediated by K(+) channels that may in turn hinder neural transmission. From a therapeutic perspective, the potent K(+) channel blocker, 4-aminopyridine (4-AP), has demonstrated neurophysiological and functional improvements in animal models of demyelination. Clinical translation of these results was recently achieved with the advent of Fampridine PR, a modified release form of 4-AP, with phase III clinical trials that demonstrated improvement in neurological symptoms including fatigue, walking speed and strength in MS patients.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Arnold R,Huynh W,Kiernan MC,Krishnan AVdoi
10.2174/0929867322666151029104452subject
Has Abstractpub_date
2015-01-01 00:00:00pages
4366-78issue
38eissn
0929-8673issn
1875-533Xpii
CMC-EPUB-71410journal_volume
22pub_type
杂志文章,评审abstract::Dendritic cells (DCs) play a central role in the establishment of tolerance/immunity, because they activate naïve T cells (TCs). Therefore, the pharmacological modulation of DCs has become a major field of interest in immunology. A large body of literature has arisen from the studies of DC biology during immunosuppres...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867054546627
更新日期:2005-01-01 00:00:00
abstract::APN is an important zinc dependent metallo-exopeptidase; it has been considered as a suitable target for anti-cancer drug design. In this review we focus on the most effective and the most promising inhibitors of aminopeptidase N. Their binding modes to the enzyme, the attempt to explain the origin of the inhibitory a...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986708786242840
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:Monocyte chemoattractant protein-1 (MCP-1) is a member of the CC chemokine family that plays a key role in the inflammatory process. It has been broadly studied in the aspect of its role in obesity and diabetes related diseases. MCP-1 causes the infiltration of macrophages into obese adipose tissue via bindi...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170303162935
更新日期:2017-01-01 00:00:00
abstract::Many serious inflammatory disorders and nutrient deficiencies induce chronic pain, and anti-inflammatory diets have been applied successfully to modify the inflammatory symptoms causing chronic pain. Numerous scientific data and clinical investigations have demonstrated that long-term inflammation could lead to an ina...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867326666190712172015
更新日期:2020-01-01 00:00:00
abstract::Chagas disease is one of the most important parasitic diseases in Latin America, affecting 16 to 18 million people. Nifurtimox and Benznidazol are drugs that are commonly used in its treatment; however, these drugs produce several adverse reactions and are not effective in the chronic phase of the disease. Therefore, ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709788803303
更新日期:2009-01-01 00:00:00
abstract::In the hit to lead process, a drug candidate is selected from a set of potential leads by screening its binding with potential targets. This review focuses on the lead identification assays that employ a bio-chemical or bio-physical test to detect molecular recognition events between proteins and small molecules in a ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986708784872366
更新日期:2008-01-01 00:00:00
abstract::Selenium is an essential trace element. It is, however toxic at concentration little above which is required for health. Selenium is incorporated into proteins as selenocysteine, the 21(st) amino acid. Selenoproteins are found in bacteria, archaea and eukaryotes. Biochemical and physicochemical properties of selenium ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867043365053
更新日期:2004-06-01 00:00:00
abstract::Although resin-based chemistry offers many practical advantages over conventional solution phase for the synthesis of combinatorial libraries, effective monitoring of reactions conducted on the support remains a challenge. A number of techniques have been developed to enable the analysis of solid phase organic synthes...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867023368737
更新日期:2002-12-01 00:00:00
abstract::Nowadays, enzymatic therapy is a very promising line of treatment for many different diseases. There is a group of disorders and conditions, caused by fibrotic and scar processes and associated with the excessive accumulation of collagen that needs to be catabolized to normalize the connective tissue content. The huma...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666171006124236
更新日期:2019-01-01 00:00:00
abstract::In order to ascertain the role of dietary flavonoids as antioxidants in vivo it is necessary to understand the chemical nature of the absorbed forms in the circulation in vivo and how the multiplicity of research findings in vitro reflect the bioactivity of flavonoids in vivo. Only when we gain adequate information on...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867013373011
更新日期:2001-06-01 00:00:00
abstract:BACKGROUND:Pollutants are diverse chemical entities, including gases such as ozone and particulate matter PM. PM contains toxic chemicals such as polycyclic aromatic hydrocarbons (PAHs). Some PAHs can induce strong oxidative stress under UVA exposure. Pollution aggravates some skin diseases such as atopy or eczema, but...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170918123907
更新日期:2018-01-01 00:00:00
abstract::Among naturally occurring isoflavones, soy isoflavones are an important class with various biological activities. Due to their phytoestrogenic structure, their effects on the brain are profound thus making the neurobiological effects of these compounds an active area of research. One such compound is daidzein, which h...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867323666161101140214
更新日期:2017-01-01 00:00:00
abstract::The biological relevance of sulfur containing carbohydrates is gaining substantial attention. Thus the new developments, especially in the synthetic and medicinal chemistry of thio-sugars are critically important for carbohydrate drug design. New studies of biological processes including biosynthetic reactions and enz...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:
更新日期:1999-02-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is an age-related neurodegenerative disorder that is believed to have complex genetic and environmental influences in the pathogenesis, but etiologies are unidentified for most patients. Until the major causes are better defined, drug development is directed at downstream pathophysi...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867321666140916120118
更新日期:2014-01-01 00:00:00
abstract::Reversible phosphorylation is a key mechanism for regulating the biological activity of many human proteins that affect a diverse array of cellular processes, including protein-protein interactions, gene transcription, cell-cycle progression and apoptosis. Once viewed as simple house keeping enzymes, recent studies ha...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867023368836
更新日期:2002-11-01 00:00:00
abstract::Thymosin Beta-4 (Tβ4) is known as a major pleiotropic actin-sequestering protein that is involved in tumorigenesis. Tβ4 is a water-soluble protein that has different promising clinical applications in the remodeling and ulcerated tissues repair following myocardial infarction, stroke, plasticity and neurovascular remo...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867326666190716125456
更新日期:2020-01-01 00:00:00
abstract::Studies on enzyme inhibition remain an important area of pharmaceutical research since these studies have led to the discoveries of drugs useful in a variety of physiological conditions. The enzyme inhibitors can interact with enzymes and block their activity towards natural substrates. Urease inhibitors have recently...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867023369853
更新日期:2002-07-01 00:00:00
abstract::Reactive oxygen species (ROS) are widely believed to cause or aggravate several human pathologies such as neurodegenerative diseases, cancer, stroke and many other ailments. Antioxidants are assumed to counteract the harmful effects of ROS and therefore prevent or treat oxidative stress-related diseases. In this repor...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986711803414368
更新日期:2011-01-01 00:00:00
abstract::Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), the rate-limiting enzyme of cholesterol synthesis. In recent years, statins have become the major choice of treatment for hypercholesterolemia. Emerging evidence from both animal and human studies indicates that mechanisms i...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867033457205
更新日期:2003-08-01 00:00:00
abstract::Type 2 diabetes mellitus (DM) is a public health burden and its co-existence with hypertension is long established in the context of the metabolic syndrome. Both DM and hypertension are major risk factors, for end-stage renal disease, cardiovascular events and mortality. Strict blood pressure (BP) control in diabetics...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867326666191029111713
更新日期:2020-01-01 00:00:00
abstract::Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It can occur at any age, however, it becomes extremely common in the elderly, with a prevalence approaching more than 20% in patients older than 85 years. AF is associated with a wide range of cardiac and extra-cardiac complications and there...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986711796642373
更新日期:2011-01-01 00:00:00
abstract::G protein-coupled receptor (GPCR) (also known as seven-transmembrane domain receptor) superfamily represents the largest protein family in the human genome. These receptors respond to various physiological ligands such as photons, odors, pheromones, hormones, ions, and small molecules including amines, amino acids to ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/09298673113209990168
更新日期:2013-01-01 00:00:00
abstract::Infections with Mycobacterium tuberculosis, the causative agent of tuberculosis, are difficult to treat using currently available chemotherapeutics. Clinicians agree on the urgent need for novel drugs to treat tuberculosis. In this mini review, we summarize data that prompts the consideration of DNA repair-associated ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867325666180129093546
更新日期:2019-01-01 00:00:00
abstract::Small interfering RNA (siRNA) constitutes an excellent way of knocking down genes. However, it requires the use of delivery systems to reach the target cells, especially to neuronal cells. Dendrimers are one of the most widely used synthetic nanocarriers for siRNA delivery. However, due to the complexity of the dendri...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867311209024929
更新日期:2012-01-01 00:00:00
abstract::Polymyxins are polypeptide antibiotics, with a primary effect of membrane damaging due to their selective binding to the lipopolysaccharide of Gram-negative bacteria. Their nephro- and neurotoxic side effects limited their use, however, in the last decade the emergence of multidrug-resistant Gram-negative bacteria led...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/09298673113209990185
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Leukotrienes (LTs) constitute a bioactive group of polyunsaturated fatty acid (PUFA) metabolites molded by the enzymatic activity of lipoxygenase (LO) and have a pivotal role in inflammation and allergy. Evidence is accumulating both by in vitro cell culture experiments and animal tumor model studies in supp...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867326666191210104820
更新日期:2019-12-09 00:00:00
abstract::Galectins form a family of carbohydrate-binding proteins defined by their affinity for beta-galactosides containing glycoconjugates. The carbohydrate recognition domain (CRD) is responsible for the specificity of galectins for saccharides. This binding may result in modulated cell proliferation, cell death and cell mi...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986706779026219
更新日期:2006-01-01 00:00:00
abstract::This review presents a general overview of the subtype-selective dopamine receptor radioligands for in vivo imaging of dopamine receptor expression by positron emission tomography (PET). Besides the (11)C- and (18)F-labeled radioligands which are already in clinical use, a summary of subtype-selective radioligands whi...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986712802002518
更新日期:2012-01-01 00:00:00
abstract::In the long human tradition honey has been used not only as a nutrient but also as a medicine. Its composition is rather variable and depends on the floral source and on external factors, such as seasonal, environmental conditions and processing. In this review, specific attention is focused on absorption, metabolism,...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986713804999358
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:The possibilities of treatment for oncological diseases are growing enormously in the last decades. Unfortunately, these developments have led to the onset of resistances with regards to the new treatments. This is particularly true if we face with the therapeutic field of Tyrosine Kinase Inhibitors (TKIs). ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867325666180607092451
更新日期:2019-01-01 00:00:00