The Bcl-2 family of proteins and their actions within the molecular machinery of cell death

Abstract

It is quite clear that understanding the actions of the Bcl-2 family of proteins within the cell death machinery is rapidly and continuously growing, but it is far from complete, and the challenge of converting that understanding into new therapeutic modalities has only begun to be approached. How do we define the multiple forms of cell death? What are the differences and similarities between apoptosis and the classical primary necrosis? What are the multiple pathways of apoptosis? Why is apoptosis important physiologically and pathologically? What are the Bcl-2 family proteins and how their structural characteristics dictate their actions within the cell death machinery? Why is regulation of mitochondrial function by Bcl-2 family proteins important in apoptotic cell death? What are the roles of the Bcl-2 family proteins in the physiological and pathological cell death in the nervous system? Those are the questions this chapter considers. Further studies of the Bcl-2 family of proteins and mechanisms of apoptotic cell death will likely reveal a complex and central role for these proteins in mediating signals for cell death and survival. Insights into the functional roles of the protective, as well as the destructive genes of the Bcl-2 family and their molecular mechanisms in various organ systems may provide promising avenues for novel therapeutic approaches to control cell death that occurs in a variety of disease and injury conditions.