Adenosine acts as neuromodulator in the brain, which its involvement in a wide range of brain processes and diseases has been studied, such as epilepsy, sleep, anxiety, panic disorder, Alzheimer’s disease, Parkinson’s disease and schizophrenia. Adenosine receptors have been detected: A1R, A2AR (A2AR), A2BR, and A3R. A1R and A2R inhibit cAMP production, while A2AR and A2BR stimulate cAMP product...

Apoptosis or programmed cell death is a gene regulated phenomenon which is important in both physiological and pathological conditions. It is characterized by distinct morphological features including chromatin condensation, cell and nuclear shrinkage, membrane blebbing and oligonucleosomal DNA fragmentation. Although, two major apoptotic pathways including 1) the death receptor (extrinsic) and...

TRAIL is a promising therapeutic agent for human malignancies. TRAIL often requires mitochondrial dysfunction, referred to as the Type II death receptor pathway, to promote cytotoxicity. However, numerous malignant cells are TRAIL resistant due to inhibition of this mitochondrial pathway. Using cholangiocarcinoma cells as a model of TRAIL resistance, we found that Hedgehog signaling blockade se...

The proper expansion and contraction of hematopoietic cells requires tight regulation of cell death. BID, a "BH3-only" molecule, amplifies death receptor signals connecting the extrinsic to intrinsic pathways by triggering the mitochondrial pathway of apoptosis. Bid-deficient mice, as they age, spontaneously develop a myeloproliferative disorder, which progresses from myeloid hyperplasia to a f...

Caspase-8 belongs to the family of cysteine proteases that plays a critical role in the regulation of programmed cell death (apoptosis). For example, caspase-8 function is required for proper signaling via the death receptor (extrinsic) pathway. Accordingly, the disturbance of caspase-8 expression or function may contribute to cancer formation and progression. In addition, inactivation of caspa...

The normal function of the extrinsic apoptotic pathway is to mediate apoptosis. Thus, this pathway is generally recognized to be critical in host immune surveillance against cancer. However, many studies have suggested that some key components in this pathway including Fas, death receptor 5 (DR5), Fas-associated death domain (FADD) and caspase-8 may contribute to cancer growth or metastasis. Ou...

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptotic cell death in a variety of tumor cells without significant cytotoxicity on normal cells. However, many cancer cells with apoptotic defects are resistant to treatment with TRAIL alone, limiting its potential as an anticancer therapeutic. Here, we report on the tumoricidal activity of a human single-chain frag...