Elias Aizenman

..1. These results suggest that Kv2.1-encoded K+ channels are necessary for the apoptotic signaling cascade in mammalian cortical neurons in culture and are sufficient for increasing the susceptibility to apoptogens in a nonexcitable cell...

..These results suggest that the alterations in NMDA receptor properties after KCN exposure may contribute to the molecular mechanisms that are activated in neurons to withstand lethal ischemic events in the brain after preconditioning...

..These results establish a direct link between microglial-generated oxygen and nitrogen reactive products and neuronal cell death mediated by intracellular Zn(2+) release and a surge in K(+) currents...

..These results indicate that neuronal Zn(2+) serves as an important, highly regulated signaling component responsible for the initiation of a neuroprotective pathway...

..These results provide new insight on the mechanism of extracellular zinc-induced toxicity in which the regulation of mitochondrial function by the Ras/MEK/ERK pathway is closely associated with neuronal viability...

..1. Our results indicate that NS5A1b limits K+ currents following injury, leading to increased neuronal viability. NS5A1b may thus serve as a model for a new generation of neuroprotective agents...

..Thus, the elevation of intracellular zinc within neurons subjected to oxidative stress can trigger a robust positive feedback loop operating through activated ERK1/2 that rapidly sets into motion a zinc-dependent pathway of cell death...

..Kv2.1-encoded channels thus regulate neuronal survival by providing a converging input for two Zn(2+)-dependent signal transduction cascades...

..These observations support a critical role for protein kinases in the rapid redistribution of neurotransmitter receptors, with profound physiological significance...

..Consequently, phosphorylation of Kv2.1 residue S800 by p38 leads to trafficking and membrane insertion during apoptosis, and remarkably, the absence of S800 phosphorylation is sufficient to prevent completion of the cell death program...

..These results suggest that GABAA receptors can be reversibly modified by a brief pulse of light via an allosteric mechanism that is intimately linked to redox modulation...

..1 channel activity and localization following ischemia. The identification of Zn(2+) in mediating ischemic modulation of Kv2.1 may lead to a better understanding of cellular adaptive responses to injury...

..Prolonged exposure to low levels of MIT and related compounds may have damaging consequences to the developing nervous system...

..Our results indicate that Cd(2+) can effectively induce transactivation of MRE in neurons by liberating Zn(2+) from its intracellular binding sites...

..We outline a neuroprotective pathway where events normally associated with apoptotic cell death are critical for cell survival...

..We conclude that KCC2 expression is not only necessary but is also sufficient for ending the depolarizing period of GABA in developing cortical neurons...

..Finally, over-expression of thioredoxin, an inhibitory binding partner of ASK1, is sufficient to halt the apoptotic current surge in neurons. Thus, ASK1 is an obligatory component of the pro-apoptotic modulation of K+ channels...

..Finally, the fifth assay details the measurement of luciferase expression as an indication of neuronal viability within a relatively small population of transfected neurons...

..Thus, redox-sensitive proteins, like metallothioneins, may play a critical role in determining neuronal cell fate by regulating the localization and concentration of intracellular free Zn(2+)...

..Modulation of the NMDA receptor by the ATD is considered within a framework of functional modularity of multisubunit ion channels. We also consider the potential importance of the ATD in assembly of the receptor...

..Emerging evidence suggests that the liberation of intracellular zinc as well as over-activation of potassium channels may be two important components of nitrosative stress-induced neuronal death...

..1 channels. Therefore, yeast-based screening has identified a novel uncharged neuroprotective mammalian K+ channel inhibitor...

..Moreover, zinc accumulation in vivo can occur in the absence of presynaptic zinc release. Together these findings suggest that accumulation of intracellular zinc is a ubiquitous component of the cell death cascade in neurons...

..Hence, light and redox modulation of the NMDA receptor may share a common intramolecular pathway for altering the function of this ion channel...

..Here we report on a method that can initially infect a single neuron-of-choice, allowing for greater precision and specificity of labeled circuits...

..Because of their widespread use, the neurotoxic consequences of both acute and chronic human exposure to these toxins need to be evaluated...

..In this review, we describe how the activation of 12-lipoxygenase and mitogen-activated protein kinase (MAPK) contribute to the toxicity of liberated zinc to neurons and oligodendrocytes...

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..These data suggest the existence of a homeostatic negative feedback loop in which increases in neuronal activity are damped by release of adenosine following activation of glutamate receptors...

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