Cell death via apoptosis is a fundamental cellular function triggered by the cell death receptor family and their ligands which signal through downstream adaptor molecules and the caspase protease family. All caspases exist in a precursor form composed of a prodomain, and large and small catalytic subunits. Caspases require a cleavage adjacent to an aspartate to liberate one large and one small subunit, which can then associate into an a2b2 tetramer. These active caspase forms are triggered by stimuli such as ligand-receptor interactions, growth factor deprivation, and cellular function inhibitors. Caspase 8 (FLICE) directly links CD95 (Fas receptor) activation into the caspase pathway, with caspase 8 overexpression inducing apoptosis. A Caspase 8 antibody was used by Berges and colleagues to characterize the role of proteosome inhibition by the inhibitor bortezomib in triggering the mitochondrial pathway of apoptosis through novel pathways in their activated T-cells1.
Studies with a Caspase 8 antibody allowed Schultz et al to evaluate the utility of AKT pathway and SPARC inhibitors as treatment regimens for glioma cell tumors with poor prognosis despite aggressive therapies2. Their promising initial data suggests that combinatory HSP27 and pAKT application is more effective than the current temozolomide (TMZ) therapy. Neurological studies out of Hermel’s group employed a Caspase 8 antibody in their studies of the autosomal dominant progressive disorder Huntington’s disease (HD), and enabled them to exclude the involvement of the subset of caspases 3, 8, and 9 in selective neuronal death3. In studies from Baylor Medical School’s Ophthalmology department, a Caspase 8 antibody enabled demonstration that topical neutralization of interferon-gamma in a desiccating stress (DS) model of dry eye syndrome preserved conjunctival goblet cells by blocking apoptosis and maintaining IL-13 signalling4. Further Caspase 8 antibody immunohistochemical studies from Herold’s group involved the establishment and validation of a novel permanent extracorporeal perfusion bioreactor system for examining fat cell apotosis5.
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