title: Neuroprotective effects of diarylpropionitrile against β-amyloid peptide-induced neurotoxicity in rat cultured cortical neurons.
abstract: 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.
authors: Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhonpathom, Thailand.
authors: Nirut
authors: N
authors: Suwanna
authors: Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhonpathom, Thailand. Electronic address: wipawan.tha@mahidol.ac.th.
authors: Wipawan
authors: W
authors: Thangnipon
authors: Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors: Rungtip
authors: R
authors: Soi-Ampornkul
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival; D002540:Cerebral Cortex / Q000187:drug effects*; D047629:Estrogen Receptor beta / Q000819:agonists; D007249:Inflammation; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000633:toxicity*; D061251:Primary Cell Culture; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D016229:Amyloid beta-Peptides; D047629:Estrogen Receptor beta; D018696:Neuroprotective Agents; D009570:Nitriles; D010446:Peptide Fragments; D011422:Propionates; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's disease; Anti-inflammation; Antioxidant; Apoptosis; Diarylpropionitrile; β-Amyloid peptide