Neuronal caspase-3 signaling: not only cell death.
Caspases are a family of cysteinyl aspartate-specific proteases that are highly conserved in multicellular organisms and function as central regulators of apoptosis. A member of this family, caspase-3, has been identified as a key mediator of apoptosis in neuronal cells. Recent studies in snail, fly and rat suggest that caspase-3 also functions as a regulatory molecule in neurogenesis and synaptic activity. In this study, in addition to providing an overview of the mechanism of caspase-3 activation, we review genetic and pharmacological studies of apoptotic and nonapoptotic functions of caspase-3 and discuss the regulatory mechanism of caspase-3 for executing nonapoptotic functions in the central nervous system. Knowledge of biochemical pathway(s) for nonapoptotic activation and modulation of caspase-3 has potential implications for the understanding of synaptic failure in the pathophysiology of neurological disorders. Fine-tuning of caspase-3 lays down a new challenge in identifying pharmacological avenues for treatment of many neurological disorders.
D'Amelio
M
M
Dulbecco Telethon Institute, Department of Biology, University of Rome Tor Vergata, Rome, Italy. m.damelio@hsantalucia.it
Cavallucci
V
V
Cecconi
F
F
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D055786:Gene Knockout Techniques; D051379:Mice; D009422:Nervous System Diseases / Q000209:etiology; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D051381:Rats; D015398:Signal Transduction
D053148:Caspase 3