Open AccessEnergy Requirement for Caspase Activation and Neuronal Cell Death
Author(s) -
Nicotera Pierluigi,
Leist Marcel,
Fava Eugenio,
Berliocchi Laura,
Volbracht Christiane
Publication year - 2000
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2000.tb00261.x
Subject(s) - caspase , apoptosis , proteases , programmed cell death , microbiology and biotechnology , nlrp1 , intrinsic apoptosis , neuropathology , caspase 8 , neuroscience , caspase 3 , caspase 10 , biology , neuroprotection , medicine , enzyme , biochemistry , disease
Recent work has shown that execution of the apoptotic program involves a relatively limited number of pathways. According to a general view, these would converge to activate the caspase family of proteases. However, there is increasing evidence that apoptotic‐like features can be found also when cells are treated with inhibitors of caspases as the cell permeable tripeptide, Z‐Val‐Ala‐Asp‐fluoromethyl‐ketone (Z‐VAD‐fmk), or analogous compounds. This has posed the question as to whether apoptosis may occur in a caspase independent way, and whether caspase inhibitors may then be used to treat diseases characterised by an excess apoptosis. It is also becoming clear, that ATP depletion during the early phases of apoptosis can preclude caspase activation, and consequently switch execution of cell death towards necrosis. In vivo, a block or partial inhibition of the typical apoptotic demise may have profound implications, as persistence of damaged but “undead” cells within the nervous system, followed by delayed lysis may favour neuroinflammatory reactions. In this review, we discuss some recent findings, which suggest that cells may use diverging execution pathways, with different implications in neuropathology and therapy.