Literature DB >> 11848681

Cholesterol-dependent gamma-secretase activity in buoyant cholesterol-rich membrane microdomains.

Suzanne Wahrle1, Pritam Das, Andrew C Nyborg, Chris McLendon, Mikio Shoji, Takeshi Kawarabayashi, Linda H Younkin, Steven G Younkin, Todd E Golde.   

Abstract

Buoyant membrane fractions containing presenilin 1 (PS1), an essential component of the gamma-secretase complex, and APP CTFbeta, a gamma-secretase substrate, can be isolated from cultured cells and brain by several different fractionation procedures that are compatible with in vitro gamma-secretase assays. Analysis of these gradients for amyloid beta protein (Abeta) and CTFgamma production indicated that gamma-secretase activity is predominantly localized in these buoyant membrane microdomains. Consistent with this localization, we find that gamma-secretase activity is cholesterol dependent. Depletion of membrane cholesterol completely inhibits gamma-secretase cleavage, which can be restored by cholesterol replacement. Thus, altering cholesterol levels may influence the development of Alzheimer's disease (AD) by influencing production and deposition of Abeta within cholesterol rich membrane microdomains.

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Year:  2002        PMID： 11848681     DOI： 10.1006/nbdi.2001.0470

Source DB:  PubMed          Journal:  Neurobiol Dis        ISSN： 0969-9961            Impact factor:   5.996


  127 in total

Review 1.  Roles for dysfunctional sphingolipid metabolism in Alzheimer's disease neuropathogenesis.

Authors:  Norman J Haughey; Veera V R Bandaru; Mihyun Bae; Mark P Mattson
Journal:  Biochim Biophys Acta       Date:  2010-05-07

2.  Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease.

Authors:  Roy G Cutler; Jeremiah Kelly; Kristin Storie; Ward A Pedersen; Anita Tammara; Kimmo Hatanpaa; Juan C Troncoso; Mark P Mattson
Journal:  Proc Natl Acad Sci U S A       Date:  2004-02-15       Impact factor: 11.205

Review 3.  Dyslipidemia and dementia: current epidemiology, genetic evidence, and mechanisms behind the associations.

Authors:  Christiane Reitz
Journal:  J Alzheimers Dis       Date:  2012       Impact factor: 4.472

4.  Altered levels and distribution of amyloid precursor protein and its processing enzymes in Niemann-Pick type C1-deficient mouse brains.

Authors:  A Kodam; M Maulik; K Peake; A Amritraj; K S Vetrivel; G Thinakaran; J E Vance; S Kar
Journal:  Glia       Date:  2010-08-15       Impact factor: 7.452

5.  Interactions of Npc1 and amyloid accumulation/deposition in the APP/PS1 mouse model of Alzheimer's.

Authors:  Ivan A Borbon; Robert P Erickson
Journal:  J Appl Genet       Date:  2010-12-18       Impact factor: 3.240

6.  Statin treatment and a disease-specific pattern of beta-amyloid peptides in Alzheimer's disease.

Authors:  Kina Höglund; Steinar Syversen; Piotr Lewczuk; Anders Wallin; Jens Wiltfang; Kaj Blennow
Journal:  Exp Brain Res       Date:  2005-06-04       Impact factor: 1.972

7.  Identification of novel γ-secretase-associated proteins in detergent-resistant membranes from brain.

Authors:  Ji-Yeun Hur; Yasuhiro Teranishi; Takahiro Kihara; Natsuko Goto Yamamoto; Mitsuhiro Inoue; Waltteri Hosia; Masakazu Hashimoto; Bengt Winblad; Susanne Frykman; Lars O Tjernberg
Journal:  J Biol Chem       Date:  2012-02-07       Impact factor: 5.157

8.  Specific Binding of Cholesterol to C99 Domain of Amyloid Precursor Protein Depends Critically on Charge State of Protein.

Authors:  Afra Panahi; Asanga Bandara; George A Pantelopulos; Laura Dominguez; John E Straub
Journal:  J Phys Chem Lett       Date:  2016-08-26       Impact factor: 6.475

9.  Effects of human apolipoprotein E isoforms on the amyloid beta-protein concentration and lipid composition in brain low-density membrane domains.

Authors:  Maho Morishima-Kawashima; Xianlin Han; Yu Tanimura; Hiroki Hamanaka; Mariko Kobayashi; Takashi Sakurai; Minesuke Yokoyama; Koji Wada; Nobuyuki Nukina; Shinobu C Fujita; Yasuo Ihara
Journal:  J Neurochem       Date:  2007-05       Impact factor: 5.372

Review 10.  Use of in vivo models to study the role of cholesterol in the etiology of Alzheimer's disease.

Authors:  Mark Burns; Karen Duff
Journal:  Neurochem Res       Date:  2003-07       Impact factor: 3.996
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