Apoptosis in nervous diseases

Apoptosis is an active mode of cell death first described in 1972 by Kerr, Currie and Wyllie. Morphological, biochemical and molecular characteristics of apoptotic cell death have been widely described, including the other parallel reviews in this issue. Among these the progressive ultrastructural changes such as compaction and segregation of nuclear chromatin, condensation of the cytoplasm, preservation of integrity and activity of cellular organelles, etc., are the most typical features of apoptotic cell death. A biochemical hallmark of apoptosis is the internucleosomal DNA cleavage operated by Ca2+-Mg2+-dependent endonucleases. Apoptosis plays a key role in physiological processes such as development and morphogenesis, maturation of the immune system and maintenance of homeostasis in actively proliferating tissues in adult organisms. However, apoptotic cell death is also involved in pathological conditions such as degenerative and neoplastic disorders of diverse tissues. Interestingly, evidence exists implicating apoptosis in a variety of chronic neurodegenerative diseases including Parkinson's, Huntington and Alzheimers diseases, amyotrophic lateral sclerosis of the familial type and others. Features of apoptotic cell death have also been described in selective neuronal populations of the central nervous system undergoing acute damage caused for instance, by ischaemia, epilepsy and trauma. Several biochemical events, including cellular free Ca2+ overloading, accumulation of different radical species, lack of neurotrophic factors and transcription of specific gene products, appear to participate in the expression of apoptotic cell death. Interestingly, in the mammalian brain pathological activation of specific receptor populations may be the trigger for these apparently independent biochemical events, ultimately leading to neuronal cell death, that may also represent the targets for newly discovered neuroprotective drugs.