title: Antioxidant and antiapoptotic effects of 1,1'-(biphenyl-4,4'-diyl)-bis(3-(dimethylamino)-propan-1-one) on protecting PC12 cells from Aβ-induced injury.
abstract: Abnormal extracellular deposition of β-amyloid (Aβ) is thought to play a key role in the pathogenesis of Alzheimer's disease (AD). Preventing Aβ-induced neurotoxicity has become a potential therapeutic approach to improve the onset and progression of AD. Here we report the synthesis of 1,1'-(biphenyl-4,4'-diyl)-bis(3-(dimethylamino)-propan-1-one) (BDBDP) and evaluate whether it protects PC12 cells from Aβ1-42-induced cytotoxicity in PC12 cells. Treating cells with Aβ1-42 significantly reduced cell viability and mitochondrial membrane potential while also significantly increasing apoptosis and production of reactive oxygen species (ROS). Pretreating the cells with BDBDP significantly ameloriated these Aβ1-42-induced effects. Futhermore, BDBDP strongly reduced pro-apoptotic signaling in response to ROS by reducing levels of activated caspase-3 and increasing the ratio of Bcl-2 to Bax. These findings provide evidence that BDBDP protects against Aβ1-42-induced neurotoxicity in PC12 cells by inhibiting oxidative stress and cell apoptosis.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University , Southern Renmin Road, No. 17, Section 3, Chengdu 610041, P. R. China.
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.forename: Qin
authors.initials: Q
authors.lastname: He
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016716:PC12 Cells; D011427:Propiophenones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats
chemical_list: C000595502:1,1'-(biphenyl-4,4'-diyl)-bis(3-(dimethylamino)propan-1-one); D016229:Amyloid beta-Peptides; D000975:Antioxidants; D001713:Biphenyl Compounds; D018696:Neuroprotective Agents; D011427:Propiophenones