Genetics of Apoptosis

8.

Evolution of cell-death principles

The driving evolutionary pressures for the development of multiple cell-death

Figure 7. Developmental cell death occurs by caspase-dependent apoptosis or by
morphologically and mechanistically distinct autophagy.

In various human diseases or animal models of them, the dominant form of neuronal disease
is, for example, dark cell death in a Huntington’s disease model, or vacuolar degeneration in
a model of amyotrophic lateral sclerosis (ALS). Selective neurite degeneration occurs
independently of caspase activation in different situations, and may eventually lead either to
caspase-dependent apoptosis of cell bodies or to nonapoptotic death with irregular chromatin
condensation. Excitotoxic death may take many forms and mechanisms depending on the
intensity of insult, the age of the animal, and the brain region affected. It often results in mixed
apoptotic and necrotic features, including cellular swelling, blebbing, nuclear pyknosis, display
of phosphatidylserine, and some autophagic processes, such as uptake of mitochondria into
lysosomes.

232 GENETICS OF APOPTOSIS