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Apoptosis in Parkinson's disease: signals for neuronal degradation.
Tatton, William G; Chalmers-Redman, Ruth; Brown, David; Tatton, Nadine.
Afiliação
  • Tatton WG; Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA. william.tatton@mssm.edu
Ann Neurol ; 53 Suppl 3: S61-70; discussion S70-2, 2003.
Article em En | MEDLINE | ID: mdl-12666099
Controversy has surrounded a role for apoptosis in the loss of neurons in Parkinson's disease (PD). Although a variety of evidence has supported an apoptotic contribution to PD neuronal loss particularly in the nigra, two factors have weighed against general acceptance: (1) limitations in the use of in situ 3' end labeling techniques to demonstrate nuclear DNA cleavage; and (2) the insistence that a specific set of nuclear morphological features be present before apoptotic death could be declared. We first review the molecular events that underlie apoptotic nuclear degradation and the literature regarding the unreliability of 3' DNA end labeling as a marker of apoptotic nuclear degradation. Recent findings regarding the multiple caspase-dependent or caspase-independent signaling pathways that mediate apoptotic nuclear degradation and determine the morphological features of apoptotic nuclear degradation are presented. The evidence shows that a single nuclear morphology is not sufficient to identify apoptosis and that a cytochrome c, pro-caspase 9, and caspase 3 pathways is operative in PD nigral apoptosis. BAX-dependent increases in mitochondrial membrane permeability are responsible for the release of mitochondrial factors that signal for apoptotic degradation, and increased BAX levels have been found in a subset of PD nigral neurons. Studies using immunocytochemistry in PD postmortem nigra have begun to define the premitochondrial apoptosis signaling pathways in the disease. Two, possibly interdependent, pathways have been uncovered: (1) a p53-glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-BAX pathway; and (2) FAS receptor-FADD-caspase 8-BAX pathway. Based on the above, it seems unlikely that apoptosis does not contribute to PD neuronal loss, and the definition of the premitochondrial signaling pathways may allow for the development and testing of an apoptosis-based PD therapy.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Parkinson / Substância Negra / Transdução de Sinais / Apoptose / Proteínas Proto-Oncogênicas c-bcl-2 / Proteínas de Arabidopsis / Degeneração Neural Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2003 Tipo de documento: Article
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Parkinson / Substância Negra / Transdução de Sinais / Apoptose / Proteínas Proto-Oncogênicas c-bcl-2 / Proteínas de Arabidopsis / Degeneração Neural Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2003 Tipo de documento: Article