Attenuation of Neuronal Death by Peptide Inhibitors of AP-1 Activation in Acute and Delayed In Vitro Ischaemia (Oxygen/Glucose Deprivation) Models |
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Authors: | Amanda J Craig Bruno P Meloni Paul Watt Neville W Knuckey |
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Institution: | (1) Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Australian Neuromuscular Research Institute, A Block, 4th floor, Nedlands, WA, Australia;(2) Department of Neurosurgery, Sir Charles Gairdner Hospital, QEII Medical Centre, Australian Neuromuscular Research Institute, Nedlands, WA, Australia;(3) Phylogica Ltd, Perth, WA, Australia;(4) QEII Medical Centre, Australian Neuromuscular Research Institute, A Block, 4th floor, Nedlands, WA, 6009, Australia; |
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Abstract: | Using acute and delayed in vitro ischaemia models we evaluated the neuroprotective efficacy of five peptides (PYC19D-TAT,
PYC35D-TAT, PYC36D-TAT, PYC38D-TAT, PYC41D-TAT) previously demonstrated to down-regulate AP-1 activation (e.g. c-Jun/c-Fos
activation), and inhibit neuronal death in vitro following glutamate and kainic acid excitotoxicity. The JNK inhibitor peptide
(JNKI-1D-TAT) and the TAT cell-penetrating-carrier peptide (D-TAT) were used as controls. In the acute model, all five AP-1
inhibitory peptides, JNKI-1D-TAT, and D-TAT provided neuroprotection by increasing neuronal viability from ≈5 to 23–53%. In
the delayed model, three of the five AP-1 inhibitory peptides (PYC35D-TAT, PYC36D-TAT, PYC38D-TAT) and JNKI-1D-TAT provided
neuroprotection by increasing neuronal viability from ≈10 to 35–80%. This study not only highlights a group of peptides with
therapeutic potential, but also the need to assess putative therapeutics in multiple in vitro models to achieve a comprehensive
representation of their neuroprotective capacity. |
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Keywords: | |
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