Concluding Remarks: New Paradigms in Excitotoxicity: Given the emerging pathogenic role played by intracellular Zn2+ accumulation in neuronal death and the fact that the ion seems to promote injury with greater potency compared to Ca2+, Zn2+ may be an underappreciated mediator of excitotoxicity, which has for the most part been thought of as a purely Ca2+-dependent phenomenon. Moreover, the deleterious effects of cytosolic [Ca2+]i increases in ischemia should perhaps be reevaluated in light of emerging data regarding the Ca2+ dependence of intracellular mobilization of Zn2+. The observation that intracellular Zn2+ release from mitochondria is particularly prominent in the case of large, glutamate-evoked [Ca2+]i rises, coupled with the likely probability that Ca2+-induced mitochondrial ROS generation would also promote Zn2+ release from MTs, offers the possibility of a more complex injury paradigm than previously imagined. In such a model, glutamate-driven [Ca2+]i rises might actually serve as an accomplice to spark the release of the true ionic mediator of neuronal damage: Zn2+.
Zinc dyshomeostasis in neuronal injury
Sensi S. L.
Ultimo
2005-01-01
Abstract
Concluding Remarks: New Paradigms in Excitotoxicity: Given the emerging pathogenic role played by intracellular Zn2+ accumulation in neuronal death and the fact that the ion seems to promote injury with greater potency compared to Ca2+, Zn2+ may be an underappreciated mediator of excitotoxicity, which has for the most part been thought of as a purely Ca2+-dependent phenomenon. Moreover, the deleterious effects of cytosolic [Ca2+]i increases in ischemia should perhaps be reevaluated in light of emerging data regarding the Ca2+ dependence of intracellular mobilization of Zn2+. The observation that intracellular Zn2+ release from mitochondria is particularly prominent in the case of large, glutamate-evoked [Ca2+]i rises, coupled with the likely probability that Ca2+-induced mitochondrial ROS generation would also promote Zn2+ release from MTs, offers the possibility of a more complex injury paradigm than previously imagined. In such a model, glutamate-driven [Ca2+]i rises might actually serve as an accomplice to spark the release of the true ionic mediator of neuronal damage: Zn2+.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
