A three amino acid peptide, Gly-Pro-Arg, protects and rescues cell death induced by amyloid β-peptide

Amyloid beta-peptide (A) contributes to the pathogenesis of Alzheimer's disease (AD), causing neuronal death through apoptosis. In this study, the neuroprotective role of small peptides, Gly-Pro-Glu (GPE), Gly-Glu (GE), Gly-Pro-Asp (GPD), and Gly-Pro-Arg (GPR) were examined against Abeta-induced toxicity in cultured rat hippocampal neurons. We report here that GPR (10-100 muM) prevented Abeta-mediated increase in lactate dehydrogenase (LDH) release and A inhibition of MTT reduction, even in neurons that were pre-exposed to A for 24 or 48 h. Since GPR prevented Abeta inhibition of MTT reduction, the anti-apoptotic effect of GPR was studied by examining activation of caspase-3 and expression of p53 protein. Caspase-3 was significantly activated by 20 muM Abeta25-35 and 5 muM Abeta1-40, but GPR effectively prevented the Abeta-mediated activation of caspase-3. Similarly, A increased numbers of p53-positive cells, but GPR prevented this Abeta effect. Our findings suggest that GPR can rescue cultured rat hippocampal neurons from Abeta-induced neuronal death by inhibiting caspase-3/p53-dependent apoptosis. (C) 2003 Elsevier Inc. All rights reserved.