Caspase-3 in the central nervous system: beyond apoptosis.
Caspase-3 has been identified as a key mediator of neuronal programmed cell death. This protease plays a central role in the developing nervous system and its activation is observed early in neural tube formation and persists during postnatal differentiation of the neural network. Caspase-3 activation, a crucial event of neuronal cell death program, is also a feature of many chronic neurodegenerative diseases. This traditional apoptotic function of caspase-3 is challenged by recent studies that reveal new cell death-independent roles for mitochondrial-activated caspase-3 in neurite pruning and synaptic plasticity. These findings underscore the need for further research into the mechanism of action and functions of caspase-3 that may prove useful in the development of novel pharmacological treatments for a diverse range of neurological disorders.
Istituto di Ricovero e Cura a Carattere Scientifico, S. Lucia Foundation, via del Fosso di Fiorano 65, 00143 Rome, Italy. m.damelio@hsantalucia.it
Marcello
M
D'Amelio
Morgan
M
Sheng
Francesco
F
Cecconi
D000544:Alzheimer Disease / Q000201:enzymology / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D053148:Caspase 3 / Q000502:physiology*; D061945:Caspase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D047108:Embryonic Development / Q000502:physiology; D004789:Enzyme Activation; D006801:Humans; D006816:Huntington Disease / Q000201:enzymology / Q000473:pathology; D036881:Long-Term Synaptic Depression / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology; D058990:Molecular Targeted Therapy; D009415:Nerve Net / Q000196:embryology / Q000201:enzymology / Q000254:growth & development; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009420:Nervous System / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development; D054259:Neural Tube / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D010300:Parkinson Disease / Q000201:enzymology / Q000473:pathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D061945:Caspase Inhibitors; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C505407:CASP3 protein, human; D053148:Caspase 3