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We have shown that quetiapine, a new antipsychotic drug, protects cultured cells against oxidative stress-related cytotoxicities induced by amyloidb (Ab)25-35, and that quetiapine prevents memory impairment and decreases Abplaques in the brains of amyloid precursor protein (APP)⁄presenilin-1 (PS-1) double-mutant mice. | ễFEBS Journal Demonstration of an anti-oxidative stress mechanism of quetiapine Implications for the treatment of Alzheimer s disease Haiyun Xu1 2 z Haitao Wang3 z Lixia Zhuang4 Bin Yan3 Yingxin Yu3 Zelan Wei3 Yanbo Zhang3 Lillian E. Dyck3 Steven J. Richardson5 Jue He3 Xiaokun Li2 Jiming Kong6 and Xin-Min Li2 3 7 1 Department of Anatomy Southern Illinois University at Carbondale IL USA 2 Laboratory of Neuropharmacology Wenzhou MedicalCollege Zhenjiang China 3 Neuropsychiatry Research Unit University of Saskatchewan Saskatoon Canada 4 Schoolof Life Science and Technology Beijing Institute of Technology China 5 Department of Pharmacology University of Saskatchewan Saskatoon Canada 6 Department of Human Anatomy and CellScience University of Manitoba Winnipeg Canada 7 Department of Psychiatry University of Manitoba Winnipeg Canada Keywords Alzheimer s disease anti-oxidant betapeptide oxidative stress quetiapine Correspondence X.-M. 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 xinmin_li@umanitoba.ca X. Li Laboratory of Neuropharmacology Schoolof PharmaceuticalScience Wenzhou Medical College Zhenjiang China Fax 86 577 86689983 Tel 86 577 8669350 E-mail xiaokunli@163.net These authors contributed equally to this work Received 29 March 2008 revised 19 May 2008 accepted 22 May 2008 doi 10.1111 j.1742-4658.2008.06519.x We have shown that quetiapine a new antipsychotic drug protects cultured cells against oxidative stress-related cytotoxicities induced by amyloid b Ab 25-35 and that quetiapine prevents memory impairment and decreases Ab plaques in the brains of amyloid precursor protein APP presenilin-1 PS-1 double-mutant mice. The aim of this study was to understand why quetiapine has these protective effects. Because the cytotoxicity of both Ab 25-35 and Ab 1-40 requires fibril formation our first experiments determined the effect of quetiapine on Ab .
