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Caspase Requirement for Neuronal Apoptosis and Neurodegeneration
Author(s) -
Nicotera Pierluigi
Publication year - 2000
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/152165400410272
Subject(s) - caspase , neurodegeneration , apoptosis , proteases , programmed cell death , intrinsic apoptosis , microbiology and biotechnology , biology , caspase 2 , xiap , neuroscience , caspase 3 , necrosis , cell , nlrp1 , disease , medicine , biochemistry , enzyme , genetics , pathology
Abstract The execution of the apoptotic programme involves a relatively few pathways that converge on activation of the caspase family of proteases. However, increasing evidence indicates that apoptoticlike features can be found also when cells are treated with inhibitors of caspases. This has posed questions as to whether death with apoptotic features can still occur in a caspase‐independent way, and whether caspase inhibitors may then be used to prevent excess apoptosis in disease. Metabolic defects, loss of neuronal connectivity and cell loss characterise several neurodegenerative diseases. Targeting excessive cell demise may be one therapeutic strategy. However, loss of connectivity and neurite regression may not be part of the apoptotic programme, and degenerating neurons might use multiple execution pathways. In addition, metabolic defects leading to ATP depletion can preclude caspase activation and consequently switch execution of cell death towards necrosis. The possibility of inhibiting apoptosis as strategy to treat neurodegenerative disease is discussed in this review.