[HTML][HTML] Cell death induction by receptors of the TNF family: towards a molecular understanding
D Wallach, M Boldin, E Varfolomeev, R Beyaert… - FEBS letters, 1997 - Elsevier
D Wallach, M Boldin, E Varfolomeev, R Beyaert, P Vandenabeele, W Fiers
FEBS letters, 1997•ElsevierIt has been known for a long time that programmed cell death (PCD) plays an essential role
in the formation of a multicellular, differentiated animal [1]. A striking example is the
development of the nematode Caenorhabditis elegans. The fully formed animal consists of
1089 cells, of which 131 are programmed to die. This system has provided a breakthrough
in understanding of the molecular processes underlying PCD. Indeed, genetic studies first
revealed the presence of genes needed for PCD, such as ced-3 and ced-4, as well as other …
in the formation of a multicellular, differentiated animal [1]. A striking example is the
development of the nematode Caenorhabditis elegans. The fully formed animal consists of
1089 cells, of which 131 are programmed to die. This system has provided a breakthrough
in understanding of the molecular processes underlying PCD. Indeed, genetic studies first
revealed the presence of genes needed for PCD, such as ced-3 and ced-4, as well as other …
It has been known for a long time that programmed cell death (PCD) plays an essential role in the formation of a multicellular, differentiated animal [1]. A striking example is the development of the nematode Caenorhabditis elegans. The fully formed animal consists of 1089 cells, of which 131 are programmed to die. This system has provided a breakthrough in understanding of the molecular processes underlying PCD. Indeed, genetic studies first revealed the presence of genes needed for PCD, such as ced-3 and ced-4, as well as other genes, such as ced-9, which counteract PCD [2]. In addition to its role in development, PCD occurs prominently in various immune processes, such as negative selection of T-cells in the thymus, elimination of overactivated lymphocytes in the periphery, etc. But PCD—or lack of it—has especially become a focus of considerable interest because of its relevance to many diseases [3]. For example, cancer cells have often become resistant to PCD-inducing stimuli, various lympho-proliferative and/or autoimmune diseases evade'death'signals, etc. On the other hand, in some neuro-degenerative disorders such as Parkinson, Alzheimer or amyotrophic lateral sclerosis, one may wish to interfere with PCD.
Cells dying in the course of development are in fact fairly difficult to study, because the cell corpses are rapidly phagocytosed by neighbouring cells. Therefore, morphological and biochemical processes associated with PCD can best be studied in cell culture systems, and the typical events leading to cell death are usually referred to as' apoptosis'.'PCD'and'apoptosis' are often used interchangeably, although the former has more a connotation of genetically predetermined, while the latter is more linked to morphological and biochemical changes [4]. The principal characteristics of apoptosis are blebbing of the plasma membrane, phosphatidylserine externalization, cytoskeletal disruption, accumulation and/or activation of transglutaminase, condensation of nuclear chromatin, fragmentation of nuclear DNA to approximately 50 kb segments, and subsequently to internucleosomal fragments; at later stages, cytoplasm and nucleus become compartmentalized and form membrane-bound apoptotic bodies, which are engulfed by neighbouring cells or infiltrated tissue macrophages [4]. Cell death by apoptosis is a very neat way to
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