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

• Treatment with DPN alleviated Aβ1–42-induced cell death and morphological changes.
• DPN also reduced production of ROS induced by Aβ1–42.
• DPN prevents Aβ1–42-induced toxicity by attenuating apoptosis and inflammation.
• DPN effects may involve inhibition of JNK and p38 including activation of ERK1/2 and Akt.

Alzheimer's disease is a major cause of dementia in the elderly that involves a β-amyloid peptide (Aβ)-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 β selective ligand, against 10 μM Aβ1–42-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-1β and IL-6 through attenuation of Aβ1–42-induced phosphorylation of mitogen-activated protein kinases JNK and p38. In addition, DPN enhanced ERK1/2 and Akt phosphorylation depressed by Aβ1–42. These findings suggest that DPN protects neurons from Aβ1–42-induced neurotoxicity through a variety of mechanisms, ranging from anti-oxidation, anti-apoptosis, through to anti-inflammation.