MECHANISMS OF APOPTOSIS AS DRUG TARGETS IN THE CENTRAL-NERVOUS-SYSTEM

Programmed cell death or apoptosis describes a process whereby cells a ctively commit to die. Under normal conditions, it is likely that apop tosis is required for embryogenesis, immune system function and tissue remodelling. Pathological conditions might lead to inappropriate inhi bition or activation of apoptosis. The former is thought to occur in t he development of cancers, while the latter might account for cellular degenerative disorders. Many central nervous system (CNS) disorders o ccur 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 overl ying 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 m echanisms that might play a role in neuronal apoptosis. In addition, t he in vitro and in vivo evidence for apoptosis in a range of central n ervous system pathologies, as well as the experimental approaches used to define the mechanisms of cell death are critically examined.