title: Protective effect of edaravone against Alzheimer's disease-relevant insults in neuroblastoma N2a cells.
abstract: Oxidative stress has been demonstrated to be involved in the pathogenesis of Alzheimer's disease (AD). Thus, antioxidant therapy may represent a promising avenue for the treatment of AD. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a potent free radical scavenger and has been shown to provide neuroprotection in both animal models of cerebral ischemia and stroke patients. In the present study, we investigated the protective effect of edaravone against AD-relevant insults in neuroblastoma N2a cells and explored the potential mechanisms involved. N2a/Swe.Δ9 cells were used as the AD model cells, which exhibited reduced cell viability, increased apoptosis and oxidative stress as well as decreased mitochondrial membrane potential compared with N2a/Wt cells. All of these phenotypes were significantly reversed by edaravone treatment. Edaravone treatment significantly elevated cell viability, reduced apoptotic rate, attenuated oxidative stress and improved mitochondrial membrane potential in N2a/Swe.Δ9 cells. Furthermore, edaravone treatment inhibited mitochondria-dependent apoptosis pathways in N2a/Swe.Δ9 cells through decreasing the Bax/Bcl-2 ratio, attenuating cytochrome c release and suppressing the activation of caspase-3. These results demonstrate that edaravone provides neuroprotection in an AD-related in vitro model and therefore, may be a potential complement for AD therapy.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Yan
authors.forename: Kai
authors.initials: K
authors.lastname: Gong
authors.forename: Tuo
authors.initials: T
authors.lastname: Ma
authors.forename: Lihai
authors.initials: L
authors.lastname: Zhang
authors.forename: Nanming
authors.initials: N
authors.lastname: Zhao
authors.forename: Xiufang
authors.initials: X
authors.lastname: Zhang
authors.forename: Peifu
authors.initials: P
authors.lastname: Tang
authors.forename: Yandao
authors.initials: Y
authors.lastname: Gong
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077553:Edaravone; D004797:Enzyme-Linked Immunosorbent Assay; D016166:Free Radical Scavengers / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D009447:Neuroblastoma; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D000077553:Edaravone; D000983:Antipyrine