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

Abramov, AY; Canevari, L; Duchen, MR; (2003) Changes in intracellular calcium and glutathione in astrocytes as the primary mechanism of amyloid neurotoxicity. J NEUROSCI , 23 (12) 5088 - 5095.

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Abstract

Although the accumulation of the neurotoxic peptide beta amyloid (betaA) in the CNS is a hallmark of Alzheimer's disease, the mechanism of betaA neurotoxicity remains controversial. In cultures of mixed neurons and astrocytes, we found that both the full-length peptide betaA (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, similar to50% 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 betaA, 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
Keywords: beta-amyloid, intracellular calcium, astrocyte, neuron, Alzheimer, glutathione, ALZHEIMERS-DISEASE, BETA-PROTEIN, HIPPOCAMPAL-NEURONS, A-BETA, CORTICAL-NEURONS, OXIDATIVE STRESS, PEPTIDE 25-35, GLIAL-CELLS, IN-VITRO, CHANNELS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
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
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: http://discovery.ucl.ac.uk/id/eprint/190607
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