Caspase-3 in the central nervous system: beyond apoptosis

• Published in: Trends in neurosciences (Regular ed.) 2012-11, Vol.35 (11), p.700-709
• Main Authors: D’Amelio, Marcello, Sheng, Morgan, Cecconi, Francesco
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - enzymology; Alzheimer Disease - pathology; Alzheimer's disease; Animals; Apoptosis; Apoptosis - physiology; Apoptosis Regulatory Proteins - physiology; Axons; Biological and medical sciences; Caspase 3 - physiology; Caspase Inhibitors - pharmacology; Caspase Inhibitors - therapeutic use; Caspase-3; Central nervous system; Differentiation; Disease Models, Animal; Embryonic Development - physiology; Enzyme Activation; Fundamental and applied biological sciences. Psychology; General aspects. Models. Methods; Human viral diseases; Humans; Huntington Disease - enzymology; Huntington Disease - pathology; Infectious diseases; long-term depression; long-term potentiation; Long-Term Synaptic Depression - physiology; Medical sciences; Mice; Mice, Knockout; Mitochondria; Mitochondria - enzymology; Molecular Targeted Therapy; Nerve Net - embryology; Nerve Net - enzymology; Nerve Net - growth & development; Nerve Tissue Proteins - physiology; Nervous system; Nervous System - embryology; Nervous System - enzymology; Nervous System - growth & development; Neural networks; Neural tube; Neural Tube - physiology; Neurodegeneration; Neurodegenerative diseases; Neurological diseases; Neurology; neuronal differentiation; Neurons - cytology; Neurons - enzymology; Parkinson Disease - enzymology; Parkinson Disease - pathology; Pharmacology; Plasticity (synaptic); Proteases; Proteinase; Receptors, N-Methyl-D-Aspartate - physiology; Reviews; synaptic loss; synaptic plasticity; Vertebrates: nervous system and sense organs; Viral diseases; Viral diseases of the nervous system
• ISSN: 0166-2236; 1878-108X
• DOI: 10.1016/j.tins.2012.06.004

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.