Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 8, Issue 4, 2008

Human C-reactive protein (CRP), injected intravenously into mice or produced inside mice by a human transgene, protects mice from death following administration of lethal numbers of Streptococcus pneumoniae. The protective effect of CRP is due to reduction in the concentration of bacteria in the blood. The exact mechanism of CRP-dependent killing of pneumococci and the partners of CRP in this process are yet to Read More

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that belongs to the proprotein convertase family. PCSK9 is synthesized as a zymogen and its prodomain is cleaved by its own catalytic activity. The cleaved prodomain forms a protein complex with the rest of the PCSK9 carboxyl terminus within the endoplasmic reticulum and is secreted. Secreted PCSK9 has been shown to be able to reduce low-density li Read More

Investigations into the role of the adenosine A2b receptor have been enigmatic due to the lack of good selective high affinity agonists and antagonists. Over the last few years several new antagonist compounds, based either on a xanthine or pyrrolpyrimidine (polyheterocyclic) structure have been designed and these have been used to localise A2b receptors in different tissues and to determine their function. Recently, a Read More

Neovascularization (NV) of the normally avascular cornea arises from various causes including inflammation, infection, trauma, and contact lens wear. Corneal NV, whatever the cause, impairs vision and threatens the survival of corneal allografts, thus representing a serious clinical problem for which treatment is limited. Recent interest has focused on vascular endothelial growth factor (VEGF), a key angiogenic factor whose Read More

Src kinase plays a key role in multiple signalling pathways regulating diverse cell functions from proliferation and survival to invasion and angiogenesis. In breast cancer, both Src protein levels and kinase activity are frequently elevated and its important role in these oncogenic processes make it a potential target for therapeutic intervention. Importantly, recent evidence has revealed a role for Src in mediating a Read More

Activation of T lymphocytes through TCR signalling takes place within the context of numerous other cell surface proteins. To prevent unnecessary activation of T cells the immune system has developed an intricate balance between positive and negative costimulatory signals. Positive costimulatory signals determine whether antigen recognition by T cells leads to full activation or to anergy/death. In contrast, the expres Read More

It has long been recognized that vitamin A and its metabolites have immune-regulatory roles but the mechanism has been unclear. Recently, there has been a significant progress in elucidating the functions of retinoic acid in regulation of immune cell development. Retinoic acid (all-trans and 9-cis retinoic acid) is produced from the cells of the intestine such as dendritic cells and provides an intestine-specific environmental cue t Read More

Crohn's disease and Ulcerative Colitis, collectively termed inflammatory bowel disease (IBD), are chronic inflammatory disorders of the bowel. It is generally accepted that the pathology associated with IBD is characterized by a hyper-reactive immune response in the gut wall directed against the commensal intestinal bacterial flora, and that the CD4+ T cells dominate the adaptive immune response. Chemokines are small prot Read More

Non alcoholic fatty liver disease (NAFLD) is defined as fat accumulation exceeding 5% to 10% by the weight of the liver, in the absence of other causes of steatosis. NAFLD is strongly associated with metabolic diseases, such as metabolic syndrome. At present, insulin resistance, elevated concentrations of free fatty acids and oxidants, and an imbalance between different cytokines have been identified as the common path Read More

Systemic hypertension, a pathological process to which the renin-angiotensin system contributes importantly, is characterized by a thrombophilic diathesis and an increased risk for acute ischemic coronary events. That apparently contradictory profile might, to some extent, relate to the modulating properties of Angiotensin II, the effector arm of the renin angiotensin system, on tissue factor expression, the physiologic init Read More