Learn More
The NMDA subtype of glutamate receptor plays an important role in the molecular mechanisms of learning, memory and excitotoxicity. NMDA receptors are highly permeable to calcium, which can lead to the activation of the calcium-dependent protease, calpain. In the present study, the ability of calpain to modulate NMDA receptor function through direct(More)
The NMDA receptor is an important target for drug development, with agents from many different classes acting on this receptor. While the severe side effects associated with complete NMDA receptor blockade have limited clinical usefulness of most antagonists, the understanding of the multiple forms of NMDA receptors provides an opportunity for development(More)
Tissue transglutaminase (tTG) is a calcium-dependent enzyme that catalyzes the posttranslational modification of proteins by transamidation of specific polypeptide-bound glutamine residues. Previous in vitro studies have demonstrated that the transamidating activity of tTG requires calcium and is inhibited by GTP. To investigate the endogenous regulation of(More)
Since excitotoxicity has been implicated in a variety of neuropathological conditions, understanding the pathways involved in this type of cell death is of critical importance to the future clinical treatment of many diseases. The N-methyl-D-aspartate (NMDA) receptor has become a primary focus of excitotoxic research because early studies demonstrated that(More)
We used ligand binding to ascertain whether the pharmacological actions of RO 25-6981 [(R:(*), S:(*))-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidinepropanol] match those of other NR2B (epsilon2) subunit specific agents. RO 25-6981 inhibited binding of 125I-MK801 [iodo-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohept-5,10-imine maleate](More)
Recent reports demonstrate that the activation and interaction of the protease calpain (CP) and the protein phosphatase calcineurin (CN) are elevated in the late stages of Alzheimer's disease (AD). However, the extent to which CPs and CN interact during earlier stages of disease progression remains unknown. Here, we investigated CP and CN protein levels in(More)
Calpains are calcium- and thiol-dependent proteases whose overactivation and degradation of various substrates have been implicated in a number of diseases and conditions such as cardiovascular dysfunction and ischemic stroke. With increasing evidence for calpain's role in cellular damage, the development of calpain inhibitors continues to be an important(More)
Mounting evidence suggests that astrocyte activation, found in most forms of neural injury and disease, is linked to the hyperactivation of the protein phosphatase calcineurin. In many tissues and cell types, calcineurin hyperactivity is the direct result of limited proteolysis. However, little is known about the proteolytic status of calcineurin in(More)
Cross-talk between calpain and caspase proteolytic systems has complicated efforts to determine their distinct roles in apoptotic cell death. This study examined the effect of overexpressing calpastatin, the specific endogenous calpain inhibitor, on the activity of the two proteolytic systems following an apoptotic stimulus. Human SH-SY5Y neuroblastoma(More)
Calpains are a family of calcium-dependent thiol-proteases which are proposed to be involved in many physiological processes as well as pathological conditions. Calpains are likely to be involved in processing of numerous enzymes and cytoskeletal components, thereby linking their activity to a variety of intracellular events. Although widely studied, the(More)