Apoptosis as a general cell death pathway in neurodegenerative diseases.
Neurodegenerative processes are generally characterized by the long-lasting course of neuronal death and the selectivity of the neuronal population or brain structure involved in the lesion. Two main common forms of cell death that have been described in neurons as in other vertebrate tissues i.e., necrosis and apoptosis. Necrosis is the result of cellular "accidents", such as those occurring in tissues subjected to chemical trauma. The necrotizing cells swell, rupture and provoke an inflammatory response. Apoptosis, on the other hand, is dependent on the cell's "decision" to commit suicide and die, and therefore is referred to as "programmed cell death" (PCD). The course of apoptotic death is characterized by a massive morphological change, including cell shrinkage, nuclear (chromosome) condensation and DNA degradation. Activation of PCD in an individual cell is based on its own internal metabolism, environment, developmental background and its genetic information. Such a situation occurs in most of the neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases and amyotrophic lateral sclerosis (ALS). In these pathological situations, specific neurons undergo apoptotic cell death characterized by DNA fragmentation, increased levels of pro-apoptotic genes and "apoptotic proteins" both, in human brain and in experimental models. It is of utmost importance to conclusively determine the mode of cell death in neurodegenerative diseases, because new "anti-apoptotic" compounds may offer a means of protecting neurons from cell death and of slowing the rate of cell degeneration and illness progression.
Offen
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D
Neurology Department and Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Rabin Medical Center, Petah-Tikva, Israel. offen_d@netvision.net.il
Elkon
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H
Melamed
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D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis; D006801:Humans; D006816:Huntington Disease / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000503:physiopathology*; D010300:Parkinson Disease / Q000503:physiopathology; D010455:Peptides / Q000235:genetics; D017096:Prion Diseases / Q000503:physiopathology
D010455:Peptides; C097188:polyglutamine