Systems Biology of Apoptosis and Survival: Implications for Drug Development

Salvatore      Pezzino; Sabrina      Paratore; Sebastiano      Cavallaro

Abstract

The advent of “systems biology” has highlighted that any function of a biological system is rarely attributable to a single molecule or a single process. Hence, complex processes, such as apoptosis and survival, depend on the activity of an integrated network of genes and their encoded proteins, which almost never work alone but interact with each other in highly structured and incredibly complex ways. With the completion of genome sequencing in humans and model organisms, and the advent of DNA microarray technology, the transcriptional cascades and gene networks regulating neuronal apoptosis and survival are being elucidated providing new potential pharmacological targets. The emerging challenge is the effective selection of the myriad of targets to identify those with the most therapeutic utility. The present review will illustrate how the identification, prioritization and validation of preclinical therapeutics can be achieved through genomic analysis of critical pathways and networks in neuronal apoptosis and survival.

Keywords: Apoptosis, drug, neuronal, pharmacogenomics, programmed cell death, survival, systems biology, target