The Nematode Caenorhabditis elegans as a Model System to Study Neuronal Cell Death

Normal development and homeostasis result from a tenuous balance between cell proliferation and cell death. Disruption of this balance, in favor of cell death in particular, could easily lead to pathological states in postmitotic organs such as the adult brain (see Thompson, 1995). For example, many neurodegenerative disorders are characterized by the premature death of specific subsets of neurons, which gives rise to their full clinical spectra (Coleman and Flood, 1987; Choi, 1988). Although a complete understanding of the selective cell degeneration in these conditions is still lacking, recent observations suggest that it may occur through apoptosis, a gene-directed type of cell death (Bredesen, 1995). In many cases, cell death by apoptosis requires an active role by the dying cells, because apoptosis is most often significantly blocked or delayed by inhibitors of RNA or protein synthesis (Wyllie et al., 1984). This genetic regulation of apoptosis offers a potential for therapeutic intervention and further assessment of apoptotic mechanisms in manifestations of neuropathology is warranted. However, employing conventional molecular and biochemical approaches, attempts to determine the genetic machinery responsible for specifying which cells live and which cells die have not always been successful in vertebrate systems.