Attenuation of Neuronal Death by Peptide Inhibitors of AP-1 Activation in Acute and Delayed In Vitro Ischaemia (Oxygen/Glucose Deprivation) Models

作者：Craig Amanda J; Meloni Bruno P^*; Watt Paul; Knuckey Neville W

来源：International Journal of Peptide Research and Therapeutics, 2011, 17(1): 1-6.

DOI：10.1007/s10989-010-9234-8

• Neuroprotection
• In vitro ischaemia
• AP-1
• JNKI
• TAT

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 a parts per thousand 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 a parts per thousand 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.

• 出版日期2011-3