Neuroprotective effects of diarylpropionitrile against β-amyloid peptide-induced neurotoxicity in rat cultured cortical neurons

Alzheimer's disease is a major cause of dementia in the elderly that involves a p-amyloid peptide (A beta)-induced cascade of an increase in oxidative damage and inflammation. The present study demonstrated the neuroprotective effects of diarylpropionitrile (DPN), a non-steroidal estrogen receptor 13 selective ligand, against 10 mu M A beta(1-42)-induced oxidative stress and inflammation in primary rat cortical cell culture. Pre-treatment with 1-100 nM DPN significantly decreased neuronal cell death by increasing cell viability through a significant attenuation in the reactive oxygen species level, downregulation of pro-apoptotic activated caspase-3 and Bax, and upregulation of anti-apoptotic Bcl-2, thereby mitigating apoptotic morphological alterations. DPN pre-treatment decreased the expression levels of pro-inflammatory cytokines IL-1 beta and IL-6 through attenuation of A beta(1-42)-induced phosphorylation of mitogen-activated protein kinases JNK and p38. In addition, DPN enhanced ERK1/2 and Akt phosphorylation depressed by A beta(1-42). These findings suggest that DPN protects neurons from A beta(1-42)-induced neurotoxicity through a variety of mechanisms, ranging from anti-oxidation, anti-apoptosis, through to anti-inflammation. (C) 2014 Elsevier Ireland Ltd. All rights reserved.