Section Review Central & Peripheral Nervous Systems: Mechanisms of apoptosis as drug targets in the central nervous system

Abstract

Programmed cell death or apoptosis describes a process whereby cells actively commit to die. Under normal conditions, it is likely that apoptosis is required for embryogenesis, immune system function and tissue remodelling. Pathological conditions might lead to inappropriate inhibition or activation of apoptosis. The former is thought to occur in the development of cancers, while the latter might account for cellular degenerative disorders. Many central nervous system (CNS) disorders occur as a result of neurodegeneration but, while it is clear that cell death observed in these conditions is a result of both apoptosis and necrosis, it is not clear to what extent each contributes to the overiying pathology. If apoptosis plays a significant role in neuronal cell death there might be therapeutic potential in targeting the apoptotic mechanisms. This review discusses some of the more recent molecular mechanisms that might play a role in neuronal apoptosis. In addition, the in vitro and in vivo evidence for apoptosis in a range of central nervous system pathologies, as well as the experimental approaches used to define the mechanisms of cell death are critically examined.