Current Drug Targets - Volume 12, Issue 9, 2011

New therapeutic strategies that focus on disease-relevant molecular events and interfere with specific signaling pathways have raised considerable expectations for the treatment of many human diseases. Forkhead box O (FOXO) proteins are emerging as transcriptional integrators of pathways that regulate a variety of cellular processes and have been considered as potential therapeutic targets for a broad range of human heal Read More

The forkhead box O (FoxO) transcription factors are known to be involved in many physiological and pathological processes including apoptosis, cell cycle arrest, stress resistance, glucose metabolism, cellular differentiation and development, and tumor suppression. The environmental cues, such as growth factors, nutrients, oxidative stress and irradiation, can either positively or negatively modulate FoxO proteins'; activities, there Read More

Hypertriglyceridemia is characterized by increased production and decreased clearance of triglyceride-rich lipoproteins including very low-density lipoprotein (VLDL) and chylomicron. Due to its proatherogenic profile, hypertriglyceridemia contributes to the development of atherosclerosis and coronary artery disease. While the pathophysiology of hypertriglyceridemia remains poorly understood, its close association with obesity Read More

FOXO transcription factors, functioning downstream of the PI3K-PTEN-AKT (PKB) signalling cascade, are essential for cell proliferation, differentiation, DNA damage repair and apoptosis. Recent research indicates that the related transcription factor FOXM1 is a direct target of repression by FOXO proteins. Inactivation of FOXO or overexpression of FOXM1 is associated with tumorigenesis and cancer progression. Read More

Forkhead FoxO transcription factors exert critical biological functions in response to genotoxic stress. In mammals four FoxOs proteins are known. FoxOs induce cell cycle arrest, repair damaged DNA, or initiate apoptosis by modulating genes that control these processes. In particular, FoxO proteins are critical regulators of oxidative stress by modulating the expression of several anti-oxidant enzyme genes. This function of F Read More

Forkhead O transcription factors (FOXO) are critical for the regulation of cell cycle arrest, cell death, and DNA damage repair. Inactivation of FOXO proteins may be associated with tumorigenesis, including breast cancer, prostate cancer, glioblastoma, rhabdomyosarcoma, and leukemia. Accumulated evidence shows that activation of oncogenic pathways such as phosphoinositide-3-kinase/AKT/IKK or RAS/mitogen-activate Read More

All fundamental reproductive events in the human ovary and uterus, including ovulation, implantation and menstruation, are dependent upon profound tissue remodelling, characterized by cyclical waves of cell proliferation, differentiation, recruitment of inflammatory cells, apoptosis, tissue breakdown and regeneration. Although the rise and fall in ovarian hormones, estradiol and progesterone, orchestrate these repro Read More

The Forkhead Box O (Foxo) proteins represent an evolutionarily conserved family of transcription factors that play an important role in regulating processes including metabolism, longevity, and cell death/survival. How is it that a single transcription factor can initiate such divergent cellular responses? We will review the evidence that specific patterns of post-translational modifications play a key role in directing Foxo into var Read More

The promotion of cellular survival, dedifferentiation, and uncontrolled proliferation via the suppression of apoptotic effectors is a fundamental characteristic of tumor cells. As substrates that are negatively regulated by oncogenic signaling cascades driven by AKT, SGK (serum- and glucocorticoid-inducible kinase), IkB kinase (IKK), ERK, and cyclin-dependent kinases (CDK), forkhead box-class O (FOXO) transcription fa Read More

FOXO transcription factors control proliferation, apoptosis, differentiation and metabolic processes. Loss of FOXO function has been identified in several human cancers, and results in increased cellular survival and a predisposition to neoplasia, especially in epithelial cancer. FOXO factors are therefore bona fide tumor suppressors, and their potential use as therapeutic targets in cancer has been a matter of debate. Importantl Read More

Until recently, nitrite has been considered a stable and inert metabolite of nitric oxide (•NO) metabolism. This view is now changing as it has been shown that nitrite can be reduced back to •NO and thus one may consider a reversible interaction regarding ˙NO:nitrite couple. Not only physiological regulatory actions have been assigned to nitrite but also may represent, in addition to nitrate, the largest ˙NO reservoir in t Read More

The advent of the biological era has seen many improvements in the management of inflammatory bowel disease (IBD). These agents, however, are not a ubiquitous panacea as they are neither universally available nor are they universally efficacious in the short or long-term. There is, therefore, still a need for other therapies and it is important to remember about the medications that have been effective in the past. T Read More