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Changes in intracellular calcium and glutathione in astrocytes as the primary mechanism of amyloid neurotoxicity

Abramov, A.Y.; Canevari, L.; Duchen, M.R.; (2003) Changes in intracellular calcium and glutathione in astrocytes as the primary mechanism of amyloid neurotoxicity. Nature Chemical Biology , 23 (12) pp. 5088-5095. Green open access

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Abstract

Although the accumulation of the neurotoxic peptide {beta} amyloid ({beta}A) in the CNS is a hallmark of Alzheimer's disease, the mechanism of {beta}A neurotoxicity remains controversial. In cultures of mixed neurons and astrocytes, we found that both the full-length peptide {beta}A (1–42) and the neurotoxic fragment (25–35) caused sporadic cytoplasmic calcium [intracellular calcium ([Ca2+]c)] signals in astrocytes that continued for hours, whereas adjacent neurons were completely unaffected. Nevertheless, after 24 hr, although astrocyte cell death was marginally increased, ~50% of the neurons had died. The [Ca2+]c signal was entirely dependent on Ca2+ influx and was blocked by zinc and by clioquinol, a heavy-metal chelator that is neuroprotective in models of Alzheimer's disease. Neuronal death was associated with Ca2+-dependent glutathione depletion in both astrocytes and neurons. Thus, astrocytes appear to be the primary target of {beta}A, whereas the neurotoxicity reflects the neuronal dependence on astrocytes for antioxidant support.

Type: Article
Title: Changes in intracellular calcium and glutathione in astrocytes as the primary mechanism of amyloid neurotoxicity
Identifier: PMID: 12832532
Open access status: An open access version is available from UCL Discovery
Publisher version: http://www.jneurosci.org/cgi/content/abstract/23/1...
Language: English
Additional information: Published by the Society of Neuroscience
Keywords: β-amyloid, intracellular calcium, astrocyte, neuron, alzheimer, glutathione
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10313
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