Chapter 1 Neuronal cell death: An updated view

Abstract

Publisher Summary It has been known for some time that apoptotic death of neurons occurs during the development of neuronal tissues in most, if not all, species. Recently, various types of evidence, morphological and biochemical, have suggested that this type of death is involved in neurodegenerative disorders ranging from stroke to Alzheimer's disease. What is now needed is some clear evidence that blocking apoptosis will have a therapeutic impact on a neurological disorder. In order to accomplish this, this chapter provides a clearer understanding of intracellular changes that accompany cell death in pathological situations. Several systems have been established to study neuronal cell death, and it has emerged that there are two general ways by which neurons can die by apoptosis. The first, represented by NGF withdrawal from SCG neurons or by a low K + shift of CGNs, is dependent on gene transcription and seems to make use of particular cytoplasmic signalling cascades, including the one that activates the transcription factor c-jun. The second, produced by staurosporine, is independent of protein synthesis and represents an activation of pre-existing cytoplasmic components. Both types of death look very much alike, from a morphological and biochemical view. Both involve caspases and both may utilize cytochrome c as a “reactive intermediate.” However, the exact nature of the proteolytic cascade seems to depend very much on the type of cell and the way in which death is induced. Recently, two papers have suggested that caspase inhibitors have the ability to decrease infarct size following ischemia/reperfus in rodent brain.