Caspases, initially identified as a family of proteases regulating cell death, 
have been found to have nonapoptotic functions as well. Some family members are 
critical for mediating programmed cell death in development. After development, 
caspases are downregulated in the nervous system, but continue to perform 
important nonapoptotic functions relevant for neurogenesis and synaptic 
plasticity. In neurodegenerative diseases, where aberrant neuronal death is an 
outstanding feature, there is an increase in caspase activity. The specific 
caspase death pathways leading to dysfunction and death have still not been 
fully clarified, despite the plethora of scientific literature addressing these 
issues. In this chapter, we will present the current knowledge of caspase 
activation and activity pathways, the current tools for examining caspases, and 
functions of caspases in the nervous system in health and in disease. 
Alzheimer's Disease, the most common neurodegenerative disorder, and cerebral 
ischemia, the most common cause of neurologic death, are used to illustrate our 
current understanding of death signaling in neurodegenerative diseases. A better 
understanding of how caspases function in health and disease would provide 
appropriate specific targets for the development of therapeutic interventions 
for these diseases. Life and death are exquisitely regulated at the cellular 
level from development through maturity. During development, neuronal death is 
the major factor shaping the nervous system. This death is mainly 
caspase-mediated apoptosis. Once the waves of developmental death have passed 
(death occurs at different times in different parts of the nervous system), 
there is downregulation of the death machinery, as the postmitotic neurons 
should live for the life of the organism. Aberrant neuronal death is a major 
part of neurodegenerative disorders, but there is still no clear understanding 
of the processes leading to the phenotypes of the various diseases. Even the 
type of death that occurs continues to be debated, whether it is apoptotic, 
necrotic, or autophagic, or some combination of these death mechanisms. Here, we 
will discuss the role that the caspases play in neuronal function, dysfunction, 
and death. First, we will discuss the regulation of caspase activation and 
activity. We will examine the current understanding of caspase function in 
developmental neuronal death and then illustrate the role of caspases in 
neuronal death in disease employing two diseases of neuronal loss, Alzheimer's 
Disease (AD), which is the most common chronic neurodegenerative disorder, and 
cerebral ischemia/stroke, the third most common cause of death in Western 
society, which is an acute neuronal disorder with chronic sequelae.