Membrane cholesterol enrichment prevents Aβ-induced oxidative stress in Alzheimer's fibroblasts

被引:34
|
作者
Pensalfini, Anna [1 ]
Zampagni, Mariagioia [1 ]
Liguri, Gianfranco [1 ,3 ]
Becatti, Matteo [1 ]
Evangelisti, Elisa [1 ]
Fiorillo, Claudia [1 ]
Bagnoli, Silvia [2 ]
Cellini, Elena [2 ]
Nacmias, Benedetta [2 ]
Sorbi, Sandro [2 ]
Cecchi, Cristina [1 ,3 ]
机构
[1] Univ Florence, Dept Biochem Sci, I-50134 Florence, Italy
[2] Univ Florence, Dept Neurol & Psychiat Sci, I-50134 Florence, Italy
[3] Univ Florence, Res Ctr Mol Basis Neurodegenerat, I-50134 Florence, Italy
关键词
Familial Alzheimer's disease; Fibroblasts; APP and PS-1 genes; Membrane cholesterol; Amyloid aggregate toxicity; Oxidative stress; PROTEIN AGGREGATION; AMYLOID PEPTIDE; CELL-TYPES; TOXICITY; DISEASE; OLIGOMERS; CALCIUM; SUSCEPTIBILITY; NEUROTOXICITY; PRESENILINS;
D O I
10.1016/j.neurobiolaging.2009.02.010
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
A growing body of evidence Implicates low membrane cholesterol in the pathogenesis of Alzheimer's disease (AD). Here we show that A beta 42 soluble oligomers accumulate more slowly and in reduced amount at the plasma membranes of PS-1L392V and APPV7171 fibroblasts from familial AD (FAD) patients enriched in cholesterol content than at the counterpart membranes. The A beta 42-induced production of reactive oxygen species (ROS) and the increase in membrane lipoperoxidation were also prevented by high membrane cholesterol, thus resulting in a higher resistance to amyloid toxicity with respect to control fibroblasts. On the other hand, the recruitment of amyloid assemblies to the plasma membrane of cholesterol-depleted fibroblasts was significantly increased, thus triggering an earlier and sharper production of ROS and a higher membrane oxidative injury. These results identify membrane cholesterol as being key to A beta 42 oligomer accumulation at the cell surfaces and to the following A beta 42-induced cell death in AD neurons. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:210 / 222
页数:13
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