He, Xiaokun Li, Jiming Kong, Xin-Min Li (2008) Demonstration of an anti-oxidative stress mechanism of quetiapine.The treatment of Alzheimer's disease doi:10.06519.Abstract DEMONSTRATION OF AN ANTI-OXIDATIVE STRESS MECHANISM OF QUETIAPINE Implications For The Treatment Of Alzheimer's Disease Haiyun Xu, Haitao Wang, Lixia Zhuang, Bin Yan, Yingxin Yu, Zelan Wei, Yanbo Zhang, Lillian E.Steven J.Jue He, Xiaokun Li, Jiming Kong and Xin-Min Li 1 Department of Anatomy, Southern Illinois University at Carbondale, IL, USA 2 Laboratory of Neuropharmacology, Wenzhou Medical College, Zhenjiang, China 3 Neuropsychiatry Research Unit, University of Saskatchewan, Saskatoon, Canada 4 School of Life Science and Technology, Beijing Institute of Technology, China 5 Department of Pharmacology, University of Saskatchewan, Saskatoon, Canada 6 Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Canada 7 Department of Psychiatry, University of Manitoba, Winnipeg, Canada X.Li, Department of Psychiatry, Faculty of Medicine, University of Manitoba, PZ432-771 Bannatyne Avenue, Winnipeg, Manitoba, Canada Fax: +1 204 789 3929 Tel: +1 204 787 7432 E-mail: X.Laboratory of Neuropharmacology, School of Pharmaceutical Science, Wenzhou Medical College, Zhenjiang, China Fax: +86 577 86689983 Tel: +86 577 8669350 E-mail: These authors contributed equally to this workAD, Alzheimer's disease; APD, antipsychotic drug; APP, amyloid precursor protein; A, amyloid ; EPR, electron paramagnetic resonance; HBSS, Hanks' balanced salt solution; PD, Parkinson's disease; PS-1, presenilin-1; ROS, reactive oxygen species; ThT, thioflavin T.Shown that quetiapine, a new antipsychotic drug, protects cultured cells against oxidative stress-related cytotoxicities induced by amyloid (A)25-35, and that quetiapine prevents memory impairment and decreases A plaques in the brains of amyloid precursor protein (APP)/presenilin-1 (PS-1) double-mutant mice.Aim of this study was to understand why quetiapine has these protective effects.The cytotoxicity of both A(25-35) and A(1-40) requires fibril formation, our first experiments determined the effect of quetiapine on A(25-35) aggregation.Inhibited A(25-35) aggregation in cell-free aqueous solutions and blocked the fibrillar aggregation of A(25-35), as observed under an electron microscope.Then investigated why quetiapine inhibits A(25-35) aggregation.The aggregation of A(25-35), a hydroxyl radical (OH) was released, which in turn amplified A(25-35) aggregation.Blocked OH-induced A(25-35) aggregation and scavenged the OH produced in the Fenton system and in the A(25-35) solution, as analyzed using electron paramagnetic resonance spectroscopy.Newpounds formed by quetiapine and OH were observed in MS analysis.We applied A(25-35) to PC12 cells to observe the effect of quetiapine on living cells.Increased levels of intracellular reactive oxygen species and calcium in PC12 cells and caused cell death, but these toxic effects were prevented by quetiapine.Results demonstrate an anti-oxidative stress mechanism of quetiapine, which contributes to its protective effects observed in our previous studies and explains the effectiveness of this drug for Alzheimer's disease patients with psychiatric and behavioralplications.THIS ARTICLE SEARCH InSynergyPubMed (MEDLINE)CrossRefBy keywordsAlzheimer's diseaseanti-oxidantbeta-peptideoxidative stressquetiapineBy authorHaiyun XuHaitao WangLixia ZhuangBin YanYingxin YuZelan WeiYanbo ZhangLillian E.Read more Amgen's First Quarter 2008 Adjusted Earnings Per Share Increased 4 percent to $1.12
Get more Thailand says will keep generic drugs for cancer treatment (AFP)
