Mechanisms of neuronal cell death

Apoptosis is a mechanism of cell death that plays a fundamental role during the development of many tissues, including the central nervous system. Apoptosis has traditionally been distinguished in developing tissues on the basis of specific morphological criteria, including perinuclear chromatin condensation, cell shrinkage, and endonuclease-mediated internucleosomal DNA fragmentation into a 'ladder' pattern. More recently, the term 'apoptosis' has been used to describe the programmed biochemical pathways of cell death that accompany development, tissue injury, and degeneration. In the context of this review, apoptosis will refer to the biochemical pathways of cell death. There is accumulating evidence that acutely injured and degenerating neurons may die by a process of apoptosis, contributing to the loss of neurons observed under these conditions. The possibility that neurons may succumb under some circumstances by an active mechanism of cell death has raised interest in the regulatory pathways governing these processes. In this review, we examine recent evidence pertaining to the presence and activation of these regulatory pathways in nervous system injury and degeneration.