Journal ArticleDOI
Zinc and Excitotoxic Brain Injury: A New Model:
TLDR
A new model of zinc currents and zinc toxicity that offers expanded opportunities for zinc-selective therapeutic chelation interventions is presented, suggesting that the original translocation model was incomplete.Abstract:
It has been nearly 15 years since the suggestion that synaptically released Zn2+ might contribute to excitotoxic brain injury after seizures, stroke, and brain trauma. In the original "zinc-translocation" model, it was proposed that synaptically released Zn2+ ions penetrated postsynaptic neurons, causing injury. According to the model, chelating zinc in the cleft was predicted to be neuroprotective. This proved to be true: zinc chelators have proved to be remarkably potent at reducing excitotoxic neuronal injury in many paradigms. Promising new zinc-based therapies for stroke, head trauma, and epileptic brain injury are under development. However, new evidence suggests that the original translocation model was incomplete. As many as three sources of toxic zinc ions may contribute to excitotoxicity: presynaptic vesicles, postsynaptic zinc-sequestering proteins, and (more speculatively) mitochondrial pools. The authors present a new model of zinc currents and zinc toxicity that offers expanded opportunities for zinc-selective therapeutic chelation interventions.read more
Citations
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Journal ArticleDOI
Metals in Neurobiology: Probing Their Chemistry and Biology with Molecular Imaging
TL;DR: The brain is a singular organ of unique biological complexity that serves as the command center for cognitive and motor function and has requirements for the highest concentrations of metal ions in the body and the highest per-weight consumption of body oxygen.
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The neurobiology of zinc in health and disease
TL;DR: The use of zinc in medicinal skin cream was mentioned in Egyptian papyri from 2000 BC, and the number of biological functions, health implications and pharmacological targets that are emerging for zinc indicate that it might turn out to be 'the calcium of the twenty-first century'.
Journal ArticleDOI
Alpha-ketoglutarate dehydrogenase: a target and generator of oxidative stress
Laszlo Tretter,Vera Adam-Vizi +1 more
TL;DR: The pathological relevance of these two features of α-KGDH is discussed in this review, particularly in relation to neurodegeneration, as an impaired function of this enzyme has been found to be characteristic for several Neurodegenerative diseases.
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Traumatic brain injury: Can the consequences be stopped?
TL;DR: New insights into the subcellular mechanisms of secondary injury are discussed that have highlighted numerous potential targets for intervention and the delayed progression of deterioration of grey and white matter.
Journal ArticleDOI
Brain, aging and neurodegeneration: role of zinc ion availability.
TL;DR: The scientific debate on the role of zinc and of some zinc-binding proteins in aging and Neurodegenerative disorders, as well as on the beneficial effect of zinc supplementation in aged brain and neurodegeneration, is extensively discussed in this review.
References
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Journal ArticleDOI
Treatment with a Copper-Zinc Chelator Markedly and Rapidly Inhibits β-Amyloid Accumulation in Alzheimer's Disease Transgenic Mice
Robert A. Cherny,Craig S. Atwood,Michel Xilinas,Danielle N. Gray,Walton D. Jones,Catriona McLean,Kevin J. Barnham,Irene Volitakis,Fiona W. Fraser,Young-Seon Kim,Xudong Huang,Lee E. Goldstein,Robert D. Moir,James Lim,Konrad Beyreuther,Hui Zheng,Rudolph E. Tanzi,Colin L. Masters,Ashley I. Bush,Ashley I. Bush +19 more
TL;DR: A 49% decrease in brain Abeta deposition is reported in a blinded study of APP2576 transgenic mice treated orally for 9 weeks with clioquinol, an antibiotic and bioavailable Cu/Zn chelator, support targeting the interactions of Cu and Zn with Abeta as a novel therapy for the prevention and treatment of AD.
Journal ArticleDOI
Release of endogenous Zn2+ from brain tissue during activity.
S. Y. Assaf,S. H. Chung +1 more
TL;DR: It is demonstrated for the first time that Zn2+ is released into the extracellular space during excitation of hippocampal slices.
Book ChapterDOI
Neurobiology of zinc and zinc-containing neurons.
TL;DR: This chapter discusses separate pools of CNS zinc, which are, vesicular zinc, free zinc, and protein-bound zinc; the enzymatic zinc is, therefore, a stable pool, involved only in the specific function of the zinc-containing enzymes.
Journal ArticleDOI
The Role of Zinc in Selective Neuronal Death After Transient Global Cerebral Ischemia
TL;DR: The toxic influx of zinc may be a key mechanism underlying selective neuronal death after transient global ischemic insults and could be prevented by the intraventricular injection of a zinc chelating agent.
Journal ArticleDOI
Stimulation-induced uptake and release of zinc in hippocampal slices.
TL;DR: It is reported that the mossy-fibre neuropil and cells of origin (dentate granule cells) take up zinc preferentially, and that electrical stimulation selectively facilitates both uptake of exogenous zinc into mossY-f fibre neuro pil and release of previously incorporated 65Zn from the tissue.