A mathematical model of caspase function in apoptosis

Abstract

Caspases (cysteine-containing aspartate-specific proteases) are at the core of the cell's suicide machinery. These enzymes, once activated, dismantle the cell by selectively cleaving key proteins after aspartate residues. The events culminating in caspase activation are the subject of intense study because of their role in cancer, and neurodegenerative and autoimmune disorders. Here we present a mechanistic mathematical model, formulated on the basis of newly emerging information, describing key elements of receptor-mediated and stress-induced caspase activation. We have used mass-conservation principles in conjunction with kinetic rate laws to formulate ordinary differential equations that describe the temporal evolution of caspase activation. Qualitative strategies for the prevention of caspase activation are simulated and compared with experimental data. We show that model predictions are consistent with available information. Thus, the model could aid in better understanding caspase activation and identifying therapeutic approaches promoting or retarding apoptotic cell death.