CD81, a cell cycle regulator, is a novel target for histone deacetylase inhibition in glioma cells.

Recent advances in cancer cell biology have focused on histone deacetylase inhibitors (HDACi's) because they target pathways critical to the development and progression of disease. In particular, HDACi's can induce expression of epigenetically silenced genes that promote growth arrest, differentiation and cell death. In glioma cells, one such repressed gene is the tetraspanin CD81, which regulates cytostasis in various cell lines and in astrocytes, the major cellular component of gliomas.

The metabolic coupling of arginine metabolism to nitric oxide generation by astrocytes.

Arginine, the only known precursor of nitric oxide, enters the brain parenchyma from the blood through the endothelial cells or from the cerebral spinal fluid through the ependymal cells. Astrocytes, whose processes abut the endothelium and ependymum, take up arginine through cationic amino acid transporters and release arginine through this transport system to the synapses that astrocytes shield. Some of these synapses are excitatory, and liberate glutamate into the synaptic cleft.

Remodeling chromatin and stress resistance in the central nervous system: histone deacetylase inhibitors as novel and broadly effective neuroprotective agents.

Acetylation and deacetylation of histone protein plays a critical role in regulating gene expression in a host of biological processes including cellular proliferation, development, and differentiation. Accordingly, aberrant acetylation and deacetylation resulting from the misregulation of histone acetyltransferases (HATs) and/or histone deacetylases (HDACs) has been linked to clinical disorders such as Rubinstein-Taybi syndrome, fragile X syndrome, leukemia, and various cancers. Of significant import has been the development of small molecule HDAC inhibitors that permit pharmacological manipulation of histone acetylation levels and treatment of some of these diseases including cancer.