Mechanisms of Disease: new therapeutic strategies for Alzheimer's disease - targeting APP processing in lipid rafts

被引：81

作者：

Cheng, Haipeng ^{[1
]}

Vetrivel, Kulandaivelu S. ^{[1
]}

Gong, Ping ^{[1
]}

Meckler, Xavier ^{[1
]}

Parent, Angele ^{[1
]}

Thinakaran, Gopal ^{[1
]}

机构：

[1] Univ Chicago, Dept Neurobiol, Chicago, IL 60637 USA

来源：

NATURE CLINICAL PRACTICE NEUROLOGY | 2007年 / 3卷 / 07期

关键词：

Alzheimer's disease; amyloid; amyloid precursor protein; cholesterol; li; pid rafts;

D O I：

10.1038/ncpneuro0549

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Alzheimer's disease (AD) is the most common cause of age- related dementia. Pathologically, AD is characterized by the deposition in the brain of amyloid-beta peptides derived from proteolysis of amyloid precursor protein (APP) by beta-site APP cleaving enzyme 1 (BACE1) and gamma-secretase. A growing body of evidence implicates cholesterol and cholesterol- rich membrane microdomains in amyloidogenic processing of APP. Here, we review recent findings regarding the association of BACE1, gamma-secretase and APP in lipid rafts, and discuss potential therapeutic strategies for AD that are based on knowledge gleaned from the membrane environment that fosters APP processing.

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收藏

页码：374 / 382

页数：9

相关论文

共 58 条

[1] Neuronal membrane cholesterol loss enhances amyloid pepticle generation [J].

Abad-Rodriguez, J ;

Ledesma, MD ;

Craessaerts, K ;

Perga, S ;

Medina, M ;

Delacourte, A ;

Dingwall, C ;

De Strooper, B ;

Dotti, CG .

JOURNAL OF CELL BIOLOGY, 2004, 167 (05) :953-960

[2] ADAMs family members as amyloid precursor protein α-secretases [J].

Allinson, TMJ ;

Parkin, ET ;

Turner, AJ ;

Hooper, NM .

JOURNAL OF NEUROSCIENCE RESEARCH, 2003, 74 (03) :342-352

[3]

Alzheimer A., 1907, ALLG Z PSYCHIAT, V64, P146, DOI DOI 10.1002/CA.980080612

[4] Post-translational processing of β-secretase (β-amyloid-converting enzyme) and its ectodomain shedding -: The pro- and transmembrane/cytosolic domains affect its cellular activity and amyloid-β production [J].

Benjannet, S ;

Elagoz, A ;

Wickham, L ;

Mamarbachi, M ;

Munzer, JS ;

Basak, A ;

Lazure, C ;

Cromlish, JA ;

Sisodia, S ;

Checler, F ;

Chrétien, M ;

Seidah, NG .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (14) :10879-10887

[5] Functions of lipid rafts in biological membranes [J].

Brown, DA ;

London, E .

ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 1998, 14 :111-136

[6] EphrinB ligands recruit GRIP family PDZ adaptor proteins into raft membrane microdomains [J].

Brückner, K ;

Labrador, JP ;

Scheiffele, P ;

Herb, A ;

Seeburg, PH ;

Klein, R .

NEURON, 1999, 22 (03) :511-524

[7] Alzheimer's disease and cholesterol: The fat connection [J].

Canevari, Laura ;

Clark, John B. .

NEUROCHEMICAL RESEARCH, 2007, 32 (4-5) :739-750

[8] Statins cause intracellular accumulation of amyloid precursor protein, β-secretase-cleaved fragments, and amyloid β-peptide via an isoprenoid-dependent mechanism [J].

Cole, SL ;

Grudzien, A ;

Manhart, IO ;

Kelly, BL ;

Oakley, H ;

Vassar, R .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (19) :18755-18770

[9] Exclusively targeting β-secretase to lipid rafts by GPI-anchor addition up-regulates β-site processing of the amyloid precursor protein [J].

Cordy, JM ;

Hussain, I ;

Dingwall, C ;

Hooper, NM ;

Turner, AJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (20) :11735-11740

[10] The role of seladin-1/DHCR24 in cholesterol biosynthesis, APP processing and Aβ generation in vivo [J].

Crameri, A ;

Biondi, E ;

Kuehnle, K ;

Lütjohann, D ;

Thelen, KM ;

Perga, S ;

Dotti, CG ;

Nitsch, RM ;

Ledesma, MD ;

Mohajeri, MH .

EMBO JOURNAL, 2006, 25 (02) :432-443

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