title: Therapeutic efficacy of stemazole in a beta-amyloid injection rat model of Alzheimer's disease.
abstract: Alzheimer's disease is one of the most devastating neurodegenerative disorders and is characterized by severe memory and cognitive decline. The deposition of beta-amyloid (Aβ) protein is the primary pathology associated with Alzheimer's disease. Current treatments for Alzheimer's disease only offer limited symptomatic alleviation, and more effective therapies are needed for Alzheimer's disease. Our primary data showed that stemazole, a novel small molecule, protected SH-SY5Y cells from toxicity induced by hydrogen peroxide and Aβ aggregates in vitro. In this study, we evaluated the therapeutic effects of a 14-day stemazole treatment in Aβ1-40 aggregate injection rat model of Alzheimer's disease. Administration of stemazole reversed learning and memory deficits induced by the Aβ1-40 aggregates in a dose-dependent manner, as assessed by a Morris water maze task. In addition, the number of Aβ1-40 aggregates was reduced in the hippocampus, as demonstrated by micro-positron emission tomography/computerized tomographic scanning. Finally, stemazole treatment reduced degeneration and the loss of neurons in the hippocampus, as shown by histology and immunohistochemical analysis. The neuroprotective effects of stemazole may be important for its therapeutic efficacy. These results demonstrate that stemazole is effective in the treatment of Aβ1-40 aggregates injection rat model, suggesting that this compound may be used as a therapeutic agent against Alzheimer's disease.
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, China. hanmeibnu@gmail.com
authors.forename: Mei
authors.initials: M
authors.lastname: Han
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Qi
authors.initials: Q
authors.lastname: Tan
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Zhang
authors.forename: Yong-Yan
authors.initials: YY
authors.lastname: Wang
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Zhang
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000473:pathology; D018891:Dentate Gyrus / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006834:Hydrazines / Q000494:pharmacology* / Q000627:therapeutic use; D007267:Injections; D008569:Memory Disorders / Q000150:complications / Q000188:drug therapy; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010069:Oxadiazoles / Q000494:pharmacology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D055503:Protein Multimerization / Q000187:drug effects; D017433:Protein Structure, Secondary; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016229:Amyloid beta-Peptides; D006834:Hydrazines; D018696:Neuroprotective Agents; D010069:Oxadiazoles; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C559095:hydrazinecarbothioamide,N-(4-(4,5-dihydro-5-thioxo-1,3,4-oxadiazol-2-yl)phenyl)