THE ROLE OF INDUCIBLE TRANSCRIPTION FACTORS IN APOPTOTIC NERVE-CELL DEATH

Recent studies have shown that certain types of nerve cell death in th e brain occur by an apoptotic mechanism. Researchers have demonstrated that moderate hypoxic-ischemic (HI) episodes and status epilepticus ( SE) can cause DNA fragmentation as well as other morphological feature s of apoptosis in neurons destined to die, whereas more severe HI epis odes lead to neuronal necrosis and infarction. Although somewhat contr oversial, some studies have demonstrated that protein synthesis inhibi tion prevents HI-and SE-induced nerve cell death in the brain, suggest ing that apoptotic nerve cell death in the adult brain is de novo prot ein synthesis-dependent (i.e., programmed). The identity of the protei ns involved in HI-and SE-induced apoptosis in the adult brain is uncle ar, although based upon studies in cell culture, a number of potential cell death and anti-apoptosis genes have been identified. In addition , a number of studies have demonstrated that inducible transcription f actors (ITFs) are expressed for prolonged periods in neurons undergoin g apoptotic death following HI and SE. These results suggest that prol onged expression of ITFs (in particular c-jun) may form part of the bi ological cascade that induces apoptosis in adult neurons. These variou s studies are critically discussed and in particular the role of induc ible transcription factors in neuronal apoptosis is evaluated.