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Psychologie & NeuroPsychiatrie du vieillissement

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Voies de signalisation intracellulaires, apoptose et pathologies neurodégénératives Volume 2, issue 3, Septembre 2004

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Laboratoire EPHE de motilité cellulaire, UMR5539, Université des sciences Montpellier II, marcilhac@univ-montp2.fr

Progressive regional loss of neurons underlies the irreversible pathology of various neurodegenerative brain diseases. In mature organisms, neurons die either by necrosis or apoptosis. Apoptotic neuronal cell death is the cardinal feature of aging and neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases, but its mechanisms remain unsolved. Cysteine proteases like caspases are known to be critical effectors in the central nervous system cellular apoptosis. More recently, the calcium-dependant protease, calpains, have been implicated in cellular apoptotic processes. Moreover, for most neurodegenerative diseases, aggregation of full lenght or truncated proteins is central but the mechanisms involved still remain a mystery. With the identification of the mechanisms which promote or prevent cell apoptosis, new approaches for preventing and treating neurodegenerative disorders could be proposed. This article reviews our understanding of intracellular signaling pathways which lead to apoptosis in the nervous system, concentrating on its possible roles in chronic neurodegenerative disorders.