title: Caspase-3 activation as a bifurcation point between plasticity and cell death.
abstract: Death-mediating proteases such as caspases and caspase-3 in particular, have been implicated in neurodegenerative processes, aging and Alzheimer's disease. However, emerging evidence suggests that in addition to their classical role in cell death, caspases play a key role in modulating synaptic function. It is remarkable that active caspases-3, which can trigger widespread damage and degeneration, aggregates in structures as delicate as synapses and persists in neurons without causing acute cell death. Here, we evaluate this dichotomy, and discuss the hypothesis that caspase-3 may be a bifurcation point in cellular signaling, able to orient the neuronal response to stress down either pathological/apoptotic pathways or towards physiological cellular remodeling. We propose that temporal, spatial and other regulators of caspase activity are key determinants of the ultimate effect of caspase-3 activation in neurons. This concept has implications for differential roles of caspase-3 activation across the lifespan. Specifically, we propose that limited caspase-3 activation is critical for synaptic function in the healthy adult brain while chronic activation is involved in degenerative processes in the aging brain.
authors.affiliation: Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, California 92697-4540, USA. ssnigdha@uci.edu
authors.forename: Shikha
authors.initials: S
authors.lastname: Snigdha
authors.forename: Erica D
authors.initials: ED
authors.lastname: Smith
authors.forename: G Aleph
authors.initials: GA
authors.lastname: Prieto
authors.forename: Carl W
authors.initials: CW
authors.lastname: Cotman
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000201:enzymology; D053148:Caspase 3 / Q000378:metabolism*; D016923:Cell Death; D006801:Humans; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000201:enzymology; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000201:enzymology*
chemical_list: D053148:Caspase 3