Systems Modelling identifies key switches between cell death and survival during neuronal energy crisis

A study by David Davila, Niamh M. C. Connolly, Helena Bonner, Petronela Weisová, Heiko Dussmann, Caoimhín G. Concannon, Heinrich J. Huber and Jochen H. M. Prehn was accepted to the high profile journal Cell Death and Differentiation in March 2012. The study involved collaboration between the Centre for Systems Medicine (computational modelling) and the Centre for the Study of Neurological Disorders (biological experimentation). The authors investigated the molecular signalling pathways mediating the apoptotic response of neurons undergoing excitotoxic stress, a process implicated in stroke and neurodegenerative diseases. Systems analysis identified a key network motif (known as a coherent feed-forward loop) that prevents apoptosis during physiological or short-term stress, but translates pathological long-term stress into robust apoptosis activation. This molecular framework thus provides a mechanism for cell fate decision making.