Effects of 17-allylamino-17-demethoxygeldanamycin (17-AAG) in transgenic mouse models of frontotemporal lobar degeneration and Alzheimer’s disease
作者机构：Department of SurgeryThe University of Hong KongPokfulamHong KongChina School of Biomedical Sciences(Pharmacology)The University of NottinghamNottinghamUK Department of MicrobiologyThe University of Hong KongPokfulamHong KongChina School of Public Health and Primary CareThe Chinese University of Hong KongShatinHong KongChina School of PharmacyThe Chinese University of Hong KongShatinHong KongChina
出 版 物：《Translational Neurodegeneration》 (转化神经变性病（英文）)
年 卷 期：2013年第2卷第1期
页 面：174-182页
基 金：This work was supported by Alzheimer’s Drug Discovery Foundation grant 271217 AFTD
主 题：Dementia Mouse Tangles Plaques
摘 要：Alzheimer’s disease(AD),the most common dementia,is characterized by potentially neurotoxic aggregation of Aβ peptide and tau protein,and their deposition as amyloid plaques and neurofibrillary tangles(NFTs).Tau aggregation also occurs in other common neurodegenerative *** dementia(FTD)can be caused by tau mutations that increase the susceptibility of tau to hyperphosphorylation and aggregation,which may cause neuronal dysfunction and deposition of NFTs.17-allylamino-17-demethoxygeldanamycin(17-AAG)is a potent inhibitor of heat shock protein 90(Hsp90),a cytosolic chaperone implicated in the proper folding and functions of a repertoire of client proteins.17-AAG binds to Hsp90 and enhances degradation of Hsp90 client *** sought to determine whether 17-AAG can reduce Aβ and tau pathology in the brains of AD and FTD model mice expressing Aβ or P301L mutant tau,*** were randomized to receive 25,5,or 0 mg/kg 17-AAG thrice weekly from age eight to 11 *** was performed by rotarod test on motor function,on the area occupied by plaques in hippocampus or NFTs in medulla tissue sections,and on mortality.A high dose of 17-AAG tended to decrease NFTs in male mice(p=0.08).Further studies are required to confirm the effect of 17-AAG in diseases of tau aggregation.
维普期刊数据库