Plant Sterols the Better Cholesterol in Alzheimer's Disease? A Mechanistical Study

被引：117

作者：

Burg, Verena K. ^{[1
]}

Grimm, Heike S. ^{[1
]}

Rothhaar, Tatjana L. ^{[1
]}

Groesgen, Sven ^{[1
]}

Hundsdoerfer, Benjamin ^{[1
]}

Haupenthal, Viola J. ^{[1
]}

Zimmer, Valerie C. ^{[1
]}

Mett, Janine ^{[1
]}

Weingaertner, Oliver ^{[3
]}

Laufs, Ulrich ^{[3
]}

Broersen, Laus M. ^{[4
]}

Tanila, Heikki ^{[5
]}

Vanmierlo, Tim ^{[6
]}

Luetjohann, Dieter ^{[6
]}

Hartmann, Tobias ^{[1
,2
]}

Grimm, Marcus O. W. ^{[1
,2
]}

机构：

[1] Univ Saarland, D-66421 Homburg, Germany

[2] Univ Saarland, Deutsch Inst DemenzPravent, D-66421 Homburg, Germany

[3] Saarland Univ Hosp, Clin Internal Med 3, D-66421 Homburg, Germany

[4] Danone Res, Ctr Specialised Nutr, Nutricia Adv Med Nutr, NL-6700 CA Wageningen, Netherlands

[5] Univ Kuopio, Dept Neurosci & Neurol, FIN-70211 Kuopio, Finland

[6] Univ Bonn, Inst Clin Chem & Clin Pharmacol, D-53105 Bonn, Germany

来源：

JOURNAL OF NEUROSCIENCE | 2013年 / 33卷 / 41期

关键词：

AMYLOID PRECURSOR PROTEIN; GAMMA-SECRETASE ACTIVITY; BETA-SECRETASE; LIPID RAFTS; A-BETA; CLEAVING ENZYME; VEGETABLE-OILS; CLATHRIN; PRESENILIN; PURIFICATION;

D O I：

10.1523/JNEUROSCI.1506-13.2013

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Amyloid-beta (A beta), major constituent of senile plaques in Alzheimer's disease (AD), is generated by proteolytic processing of the amyloid precursor protein (APP) by beta-and gamma-secretase. Several lipids, especially cholesterol, are associated with AD. Phytosterols are naturally occurring cholesterol plant equivalents, recently been shown to cross the blood-brain-barrier accumulating in brain. Here, we investigated the effect of the most nutritional prevalent phytosterols and cholesterol on APP processing. In general, phytosterols are less amyloidogenic than cholesterol. However, only one phytosterol, stigmasterol, reduced A beta generation by (1) directly decreasing beta-secretase activity, (2) reducing expression of all beta-secretase components, (3) reducing cholesterol and presenilin distribution in lipid rafts implicated in amyloidogenic APP cleavage, and by (4) decreasing BACE1 internalization to endosomal compartments, involved in APP beta-secretase cleavage. Mice fed with stigmasterol-enriched diets confirmed protective effects in vivo, suggesting that dietary intake of phytosterol blends mainly containing stigmasterol might be beneficial in preventing AD.

引用

页码：16072 / 16087

页数：16

共 79 条

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Anthrax toxin triggers endocytosis of its receptor via a lipid raft-mediated clathrin-dependent process [J].