Abstract:
:Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disease that affects largely synovial joints. It has been postulated that activated autoreactive CD4 T cells play a key role in triggering and/or maintaining the chronic inflammatory process in RA. Dendritic cells (DCs) are antigen-presenting cells that activate cognate clonal CD4 T cells in the lymph nodes. The activation process involves the formation of a molecular structure at the DC-CD4 T cell contact zone called immunological synapse (IS). In RA, the synovium, a thin layer of tissue below the capsule in the joints, shows a massive infiltration of DCs and CD4 T cells. Subjects bearing HLA-DRB1 alleles of the Major Histocompatibility Complex II gene displaying a motif called RA "shared epitope (SE)", have an enhanced susceptibility to suffer RA. Interestingly, the SE-containing HLA-DRB1 molecules display a pocket with a high affinity for citrullinated antigens, which are found at higher levels in subjects prone to develop RA. Thus, it is possible that the DCs of susceptible individuals may form IS with particular features that may present citrullinated peptides to autorreactive naïve CD4 T clones that, after being activated, contribute to the initiation or development of the disease. Herein I put forward a model of RA initiation based on current information on the immune response and RA.
journal_name
Curr Top Med Chemjournal_title
Current topics in medicinal chemistryauthors
Rodríguez-Fernández JLdoi
10.2174/1568026611313060004subject
Has Abstractpub_date
2013-01-01 00:00:00pages
712-9issue
6eissn
1568-0266issn
1873-4294pii
CTMC-EPUB-20130409-4journal_volume
13pub_type
杂志文章,评审abstract:INTRODUCTION:Mosquito borne diseases continue to propagate and cause millions of deaths annually. They are caused either by protozoan parasites such as Plasmodium, Toxoplasma or by flaviviruses including Dengue and Zika. Among the proteome of such parasitic organisms, proteases play essential roles in events such as ho...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026617666170130122231
更新日期:2017-01-01 00:00:00
abstract::Recent advances in DNA microarray technology have great impact on many areas of biomedical research and pharmacogenomics: discovering novel targets and genes, elucidating signatures of complex diseases, transcriptional profiling of models for diseases, and the development of individually optimized drugs based on diffe...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026043387773
更新日期:2004-01-01 00:00:00
abstract::Over the past decades, a tremendous rise in invasive fungal infection diseases attributed to the yeast Candida albicans in immunocompromised individuals poses a seriously challenging issue. Another concern is the emergence of multi-drug resistant pathogens to the existing medicines due to their overuse and misuse. It ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026620666200704140107
更新日期:2020-01-01 00:00:00
abstract::Diabetes mellitus type 2 (DMT2) is a metabolic disease characterized by a chronic increase in glycemia that promotes several long-term complications and high mortality. Some enzymes involved in glycaemic control, such as α -(1,4)-glucosidase, have now been established as novel pharmacological targets. Coumarins have s...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026619666181130113033
更新日期:2018-01-01 00:00:00
abstract::The H(3) histamine receptor is expressed in many brain regions, including those involved in sleep/wake regulation and cognitive functions. Inhibition of the H(3) receptor leads to increased release of multiple neurotransmitters in these regions, making this receptor an ideal target for the potential enhancement of aro...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802610790411027
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Antimicrobial research is being focused to look for more effective therapeutics against antibiotic-resistant infections caused by methicillin-resistant Staphylococcus aureus (MRSA). In this direction, antimicrobial peptides (AMP) appear as promising tool. OBJECTIVES:This study evaluated the antimicrobial ac...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026618666181022140348
更新日期:2018-01-01 00:00:00
abstract::Bacterial infections constitute an always growing health problem worldwide. The resistance to antibiotics of an increasing number of bacterial pathogens necessitates a permanent search for new molecules with different mechanisms of action. Histidine biosynthesis is an ancient pathway found in bacteria, archaebacteria,...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026616666160413140000
更新日期:2016-01-01 00:00:00
abstract::Post translational modification (PTM) is one of the critical levels in regulation of gene expression that determines the fate of proteins after translation in eukaryotic cells. Since the detection of PTM sites in proteins is useful for diagnosis and prevention of diseases, numerous web-tool predictors are introduced t...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026617666170328100908
更新日期:2017-01-01 00:00:00
abstract::Fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGL) are hydrolytic enzymes which degrade the endogenous cannabinoids (endocannabinoids) N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), respectively. Endocannabinoids are an important class of lipid messenger molecules that ar...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802610791164238
更新日期:2010-01-01 00:00:00
abstract::Gene therapy has a strong potential in neuroscience by suppressing or replacing abnormalities in genetic materials. The employment of nano-gene carrier for neurological disorders is comparatively young and restricted since the aim to effectively deliver therapeutic agents into the central nervous system (CNS) commonly...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026616666161222145654
更新日期:2017-01-01 00:00:00
abstract::R115777 (R)-6-amino[(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone is a potent and selective inhibitor of farnesyl protein transferase with significant antitumor effects in vivo subsequent to oral administration in mice. Taking its roots into Janssen's ketoconazole and...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026033452050
更新日期:2003-01-01 00:00:00
abstract::Multiple Gαi protein-coupled somatostatin receptors (SSTRs) are expressed in human kidney and liver tissues. Also, aberrant cAMP signaling has been shown to play a critical role in cysto-genesis and enlargement of the human kidney and liver. Thus, somatostatin (SST) analogs become potential and promising alternatives ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026615666150701115157
更新日期:2015-01-01 00:00:00
abstract::In recent times, the novel concept of generating hybrid molecules by pharmacophoric hybridisation approach is fast becoming an alternative to other existing strategies of drug development. These hybrids also known as 'dual drugs' or 'double drugs' are especially found to be effective in overcoming drug resistance prob...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026614666140808125728
更新日期:2014-01-01 00:00:00
abstract::Apoptosis is a vital physiological process, which is observed in various biological events. The anti-apoptotic and pro-apoptotic members of Bcl-2 family are the most characterized proteins which are involved in the regulation of apoptotic cell death. The anti-apoptotic proteins such as Bcl-2 and Bcl-xL prevent apoptos...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026619666190119144819
更新日期:2018-01-01 00:00:00
abstract::Sphingosine 1-phosphate (S1P) evokes a plethora of physiological responses by stimulating members of a G protein-coupled receptor family, known as S1P receptors. Currently five different mammalian S1P receptor subtypes, S1P₁₋₅, each with a different cellular expression pattern, were identified. The S1P₁ receptor in pa...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026611109060726
更新日期:2011-01-01 00:00:00
abstract::Thiosemicarbazones (TSCNs) constitute a broad family of compounds (R1R2C=N-NH-C(S)- NR3R4), particularly attractive because many of them display some biological activity against a wide range of microorganisms and cancer cells. Their activity can be related to their electronic and structural properties, which offer a r...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026620666201022144004
更新日期:2021-01-01 00:00:00
abstract::Pyrimidine and purine nucleosides and their derivatives have critical functions and pharmacological applications in the brain. Nucleosides and nucleobases are precursors of nucleotides, which serve as the energy-rich currency of intermediary metabolism and as precursors of nucleic acids. Nucleosides (e.g., adenosine) ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802611795347582
更新日期:2011-01-01 00:00:00
abstract::Trichomoniasis, one of the most common non-viral sexually transmitted infections worldwide, is caused by the parasite Trichomonas vaginalis. The pathogen colonizes the human urogenital tract, and the infection is associated with complications such as adverse pregnancy outcomes, cervical cancer, and an increase in HIV ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026620999200904122212
更新日期:2021-01-01 00:00:00
abstract::Urinary protein biomarkers and metabolomic markers have been leveraged to detect acute Drug Induced Kidney Injury (DIKI) in rats; however, the utility of these indicators to enable early detection of DIKI in canine models has not been well documented. Therefore, we evaluated temporal changes in biomarkers and metaboli...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026617666170713172331
更新日期:2017-01-01 00:00:00
abstract::Histone deacetylase (HDAC) inhibitors constitute a novel and growing class of anticancer agents that function by altering intracellular patterns of histone acetylation, the so-called epigenetic "histone code," thereby producing changes in cell cycle arrest, differentiation, and/or apoptosis in tumor cells. This overvi...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802608784911581
更新日期:2008-01-01 00:00:00
abstract::The first proteolytic step in the processing of amyloid precursor protein (APP) to amyloid-beta (Abeta) in the brain is performed by beta-site APP cleaving enzyme (BACE1). This enzyme is a membrane bound aspartic protease with high homology of the catalytic domain to renin and pepsin and of yet unknown physiologic fun...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026024607490
更新日期:2002-04-01 00:00:00
abstract::Since the advent of high-throughput DNA sequencing technologies, the ever-increasing rate at which genomes have been published has generated new challenges notably at the level of genome annotation. Even if gene predictors and annotation softwares are more and more efficient, the ultimate validation is still in the ob...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026613666131204105652
更新日期:2014-01-01 00:00:00
abstract::Structure-activity relationships of a 4-aminoquinoline MCH-1R antagonist lead series were explored by synthesis of analogs with modifications at the 2-, 4- and 6-positions of the original HTS hit. Improvements to the original screening lead were made by addition of lipophilic groups at the 2-position and biphenyl, cyc...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802607782194789
更新日期:2007-01-01 00:00:00
abstract::This review mainly covers last five year literature on CCK1R agonists and antagonists. These CCK1R ligands have been found following the two usual and complementary strategies for drug discovery: rational design based on structure activity relationships on the CCK-7 and CCK-4 peptide sequences of the endogenous ligand...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802607780960537
更新日期:2007-01-01 00:00:00
abstract::The increase of pathogens being resistant to antibiotics represents a global health problem and therefore it is a pressing need to develop antibiotics with novel mechanisms of action. Host defense peptides, which have direct antimicrobial activity (also termed antimicrobial peptides) or immune modulating activity, are...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:
更新日期:2017-01-01 00:00:00
abstract::Fluorine-18 ((18)F, beta(+); 96.7%, T(1/2)=109.8 min) is of considerable importance for developing positron emission tomography (PET) ligands for imaging receptor, enzyme, gene expression etc. in brain, tumor, myocardium and other regions or organs due to its optimal decay characteristics. To synthesize (18)F-labeled ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802607782507448
更新日期:2007-01-01 00:00:00
abstract::The sol-gel process provides a robust and versatile technology for the immobilization of biologicals. A wide range of inorganic, composites and hybrid materials can be prepared to encapsulate molecular drugs, proteins, antibodies/antigens, enzymes, nucleic acids, prokaryotic and eukaryotic cells into bulk gels, partic...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026614666141229112734
更新日期:2015-01-01 00:00:00
abstract::Aptamers- short nucleic acid or peptide ligands- attracted considerable attention across various disciplines as target specific therapeutic, delivery vehicle and diagnostic tools. The applicability of aptamers - often termed as 'chemical antibodies' - continues to grow and possess certain edge over the antibody counte...
journal_title:Current topics in medicinal chemistry
pub_type: 社论
doi:10.2174/1568026615666150413161707
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Development of acetyl- (AChE) and butyrylcholinesterase (BuChE) inhibitors belongs to viable strategies for the treatment of dementia and other diseases related to decrease in cholinergic neurotransmission. OBJECTIVE:That is why we designed twenty-two analogues of a dual AChEBuChE salicylanilide inhibitor, ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026620666200819154722
更新日期:2020-01-01 00:00:00
abstract::Recent advances in synthesis of functional poly-ε-caprolactone (PCL) and its self-assembly behavior, as well as application in drug delivery have been reviewed. Three strategies including end group functionalization, postpolymerization modification and new monomer preparation have been summarized to show possibilities...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026614666140118222820
更新日期:2014-01-01 00:00:00