Cyclohexanehexol inhibitors of Aβ aggregation prevent and reverse Alzheimer phenotype in a mouse model

被引:299
作者
McLaurin, JoAnne
Kierstead, Meredith E.
Brown, Mary E.
Hawkes, Cheryl A.
Lambermon, Mark H. L.
Phinney, Amie L.
Darabie, Audrey A.
Cousins, Julian E.
French, Janet E.
Lan, Melissa F.
Chen, Fusheng
Wong, Sydney S. N.
Mount, Howard T. J.
Fraser, Paul E.
Westaway, David
St George-Hyslop, Peter
机构
[1] Univ Toronto, Ctr Res Neurodegenerat Dis, Toronto, ON M5S 3H2, Canada
[2] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 3H2, Canada
[3] Univ Toronto, Dept Med, Toronto, ON M5S 3H2, Canada
[4] Univ Toronto, Univ Hlth Network, Toronto Western Hosp, Res Inst, Toronto, ON M5S 3H2, Canada
[5] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 3H2, Canada
基金
加拿大健康研究院; 加拿大自然科学与工程研究理事会;
关键词
D O I
10.1038/nm1423
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
When given orally to a transgenic mouse model of Alzheimer disease, cyclohexanehexol stereoisomers inhibit aggregation of amyloid b peptide ( Ab) into high-molecular-weight oligomers in the brain and ameliorate several Alzheimer disease-like phenotypes in these mice, including impaired cognition, altered synaptic physiology, cerebral Ab pathology and accelerated mortality. These therapeutic effects, which occur regardless of whether the compounds are given before or well after the onset of the Alzheimer disease-like phenotype, support the idea that the accumulation of Ab oligomers has a central role in the pathogenesis of Alzheimer disease.
引用
收藏
页码:801 / 808
页数:8
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