Current Drug Targets - Volume 11, Issue 8, 2010

Worldwide research activities about the role of small regulatory RNA molecules, especially microRNAs, have been exploded and promise development of more mechanistic-orientated molecular therapies of an array of diseases. One of the most important characteristics of miRNAs may be the fact the miRNAs not only regulate single genes but fine-tune complete pathways of often co-ordinately acting genes. In this Read More

The molecular biology dogma that DNA replicates its genetic information within nucleotide sequences and transcribes it to RNA where it codes for the generation of mRNA, failed to consider a significant part of the genetic code. Although it has been generally assumed that most genetic information is executed by proteins, recent evidence suggests that the majority of the genomes of mammals and other complex organis Read More

Heart ion-channel function and expression are continuously being regulated on the basis of the hemodynamic state of the cardiovascular system, the neurohumoral milieu and the properties of the ongoing ionic fluxes. These homeostatic forces act through multiple mechanisms at transcriptional, translational and post-translational levels. Of clinical importance is the fact that with adverse stress these regulatory me Read More

microRNAs (miRNAs) are powerful, recently recognized regulators of gene expression. miRNAs modulate virtually all aspects of cardiac biology, from cardiac specification and development to cardiomyocyte survival and hypertrophy. Expression profiling of experimental and human heart disease has shown that miRNA expression is altered in heart disease, and miRNA expression signatures may be useful biomarkers for he Read More

MicroRNA-21 (miR-21) expression is activated in multiple types of cancers, such as breast, liver, brain, prostate, myometrial cancers but also in cardiovascular disease. MiR-21 regulates a plethora of target proteins which are involved in cellular survival, apoptosis and cell invasiveness. MiR-21 regulation is complex due to an own promoter that is target for various transcription factors and hormones. The consistent miR-21 over Read More

MicroRNAs are small non-coding RNAs that regulate gene expression at the posttranscriptional level by either inhibiting mRNA translation or inducing mRNA degradation. These regulatory mechanisms occur in a sequence-specific manner through the direct binding of the microRNA to complementary reverse sequences in the 3' UTR of target mRNAs. The sequence-specific nature of microRNAs allows for the regulation Read More

MicroRNAs are endogenously expressed small non-coding RNAs that regulate gene expression on the posttranscriptional level. During the last years microRNAs have emerged as key regulators of several physiological and pathophysiological processes in the vascular wall. Endothelial cell functions and angiogenesis are critically regulated by microRNAs such as miR-126 and the miR-17-92 cluster in vitro and in vivo. Tumor angiogene Read More

Atherosclerosis is now widely appreciated to represent a chronic inflammatory reaction of the vascular wall in response to dyslipidemia and endothelial distress involving the inflammatory recruitment of leukocytes and the activation of resident vascular cells. The proliferative response of smooth muscle cells critically contributes to arterial remodelling. As part of the inflammatory infiltrate, monocytes/macrophages, but als Read More

Glucocorticoids are the mainstay of asthma management and effectively treat acute exacerbations of asthma. However, a small subset of asthmatics, usually with severe asthma, respond poorly even to systemic administration of high-dose glucocorticoids and this condition is termed “steroid-resistant asthma”. This cohort, although small, accounts for ~50% of total health care cost for asthma. New investigations into Read More

Kisspeptin has emerged as a critical player in the initiation of puberty and reproductive function. In humans, inactivating mutations of the kisspeptin receptor result in hypogonadotrophic hypogonadism and kisspeptin receptor activating mutations cause precocious puberty. Kisspeptin potently stimulates the release of gonadotrophins predominantly through the release of gonadotrophin-releasing hormone (GnRH). Here we revi Read More

The eye is innervated by numerous serotonergic nerves and serotonin (5-hydroxytryptamine; 5HT) is present in the aqueous humor of animal and human eyes. In an effort to delineate the role of the serotonergic system in modulating intraocular pressure (IOP) within the anterior segment of the eye, extensive topical ocular dosing studies were conducted with a variety of 5HT ligands and in various animal species. Even though Read More

Here we review phospho-specific, quantitative flow cytometry approach as a rapid and reliable tool for measuring intracellular signaling proteins with potential applications in monitoring efficacy of targeted therapy. The single cell, multiparameter nature of flow cytometry allows simultaneous investigation of specific cell type and the corresponding intracellular markers. Peripheral blood can be directly stained with surface mark Read More

New blood vessel formation (angiogenesis) is fundamental to tumor growth, invasion, and metastatic dissemination. The vascular endothelial growth factor (VEGF) signaling pathway plays pivotal roles in regulating tumor angiogenesis. VEGF as a therapeutic target has been validated in various types of human cancers. Different agents including antibodies, aptamers, peptides, and small molecules have been extensively i Read More

Aberrant folded proteins are hallmarks of amyloidogenic diseases. Examples are Alzheimer's disease (AD) and prion-related disorders (PrD). These disorders, although clinically different, have the same underlying pathogenetic mechanism: an altered protein conformer with high β-sheet structure content: the amyloid beta peptide (Aβ) in the case of AD, and the aberrant prion protein, PrPsc in PrD. Although the molecular Read More

Heart failure, the common end-point of many cardiac diseases, is a major contributor to mortality and morbidity and contributes considerably to health care costs. Current treatment regimens include β-adrenergic antagonists, angiotensin converting enzyme inhibitors, and inotropic agents are used by some patients. Studies in experimental animals have demonstrated that inhibition of signaling pathways downstream of the Read More