The scientists discovered how a region in the XIAP protein called BIR3 attaches to caspase-9 and blocks its activity. Harnessing Smac's activity or devising a drug to mimic it allows caspase activation and apoptosis to occur. Our study defines how XIAP blocks caspase-9 activity, a first step in designing and improving the efficacy of new drugs to inhibit or activate caspases. You want to activate apoptosis by activating caspases in cancer to kill the cells. In cases of neurodegenerative diseases such as Alzheimer's and Parkinson's, and others such as stroke and heart attack, you want to prevent apoptosis by inhibiting caspases.
Apoptosis is a fundamental biological process vital to cell differentiation and normal development.
In human embryos, for example, apoptosis creates fingers from mitt-like hands. It occurs during normal aging and sometimes during irreversible cell injury from radiation and other poisons. Apoptosis has received a great deal of attention in the popular press in recent years when scientists discovered that part of the reason cancer cells grow with out of control is because they lose the ability to die at a preset time. In many cancers, IAP activity abounds. One company, Idun Pharmaceuticals in San Diego, which also supports Dr. Alnemri's research, has already begun conducting clinical trials with synthetic compounds it developed to inhibit caspases.