Apoptosis in development and disease of the nervous system: 1. Naturally occurring cell death in the developing nervous system.

In recent years, apoptosis, the process by which cells orchestrate their own demise, has been the subject of increasingly intense investigation, both from the stand-point of basic mechanisms of signal transduction and with regard to its role in normal and pathological processes in the nervous system. For the neurologist, an understanding of the mechanisms by which apoptosis determines at a cellular level the normal form of the nervous system, an appreciation of how both unchecked apoptosis and failure of enactment of the apoptotic pathway contribute to nervous system pathology and a sense of how both induction and inhibition of apoptosis can be exploited therapeutically are critical to applying the basic knowledge in this field to human disease. Early studies made it clear that substances produced by the target tissue influenced the survival of developing neurons. More recent investigations have demonstrated that they do so by influencing the production of a series of endogenous mediators and modulators of neuronal survival. Furthermore, it is evident that apoptosis is important for the development of both neuronal and non-neuronal cells in the peripheral and central nervous systems.