Effect of Different Phospholipids on α-Secretase Activity in the Non-Amyloidogenic Pathway of Alzheimer's Disease

被引：31
作者：
Grimm, Marcus O. W. [1 ,2 ]
Haupenthal, Viola J. [1 ]
Rothhaar, Tatjana L. [1 ]
Zimmer, Valerie C. [1 ]
Groesgen, Sven [1 ]
Hundsdoerfer, Benjamin [1 ]
Lehmann, Johannes [1 ]
Grimm, Heike S. [1 ]
Hartmann, Tobias [1 ,2 ]
机构：
[1] Univ Saarland, D-66421 Homburg, Germany
[2] Univ Saarland, DIDP, D-66421 Homburg, Germany
来源：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2013年 / 14卷 / 03期
关键词：
Alzheimer's disease; alpha-secretase; ADAM10; lipids; phospholipids; chain length; saturation; headgroup; N-3; FATTY-ACIDS; PRECURSOR PROTEIN; GAMMA-SECRETASE; DOCOSAHEXAENOIC ACID; BETA-SECRETASE; TRANSMEMBRANE DOMAIN; MEMBRANE-LIPIDS; DHA DIET; CHOLESTEROL; CLEAVAGE;
D O I：
10.3390/ijms14035879
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Alzheimer's disease (AD) is characterized by extracellular accumulation of amyloid-beta peptide (A beta), generated by proteolytic processing of the amyloid precursor protein (APP) by beta- and gamma-secretase. A beta generation is inhibited when the initial ectodomain shedding is caused by alpha-secretase, cleaving APP within the A beta domain. Therefore, an increase in alpha-secretase activity is an attractive therapeutic target for AD treatment. APP and the APP-cleaving secretases are all transmembrane proteins, thus local membrane lipid composition is proposed to influence APP processing. Although several studies have focused on gamma-secretase, the effect of the membrane lipid microenvironment on alpha-secretase is poorly understood. In the present study, we systematically investigated the effect of fatty acid (FA) acyl chain length (10:0, 12:0, 14:0, 16:0, 18:0, 20:0, 22:0, 24:0), membrane polar lipid headgroup (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine), saturation grade and the FA double-bond position on alpha-secretase activity. We found that alpha-secretase activity is significantly elevated in the presence of FAs with short chain length and in the presence of polyunsaturated FAs, whereas variations in the phospholipid headgroups, as well as the double-bond position, have little or no effect on alpha-secretase activity. Overall, our study shows that local lipid membrane composition can influence alpha-secretase activity and might have beneficial effects for AD.
引用
收藏
页码：5879 / 5898
页数：20
相关论文
共 76 条
[1]   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
[2]   ARACHIDONIC AND DOCOSAHEXANOIC ACID CONTENT OF BOVINE BRAIN MYELIN - IMPLICATIONS FOR THE PATHOGENESIS OF MULTIPLE-SCLEROSIS [J].
ANSARI, KA ;
SHOEMAN, DW .
NEUROCHEMICAL RESEARCH, 1990, 15 (01) :7-11
[3]   Fish, meat, and risk of dementia:: cohort study [J].
Barberger-Gateau, P ;
Letenneur, L ;
Deschamps, V ;
Pérès, K ;
Dartigues, JF ;
Renaud, S .
BRITISH MEDICAL JOURNAL, 2002, 325 (7370) :932-+
[4]   The Amyloid Precursor Protein Has a Flexible Transmembrane Domain and Binds Cholesterol [J].
Barrett, Paul J. ;
Song, Yuanli ;
Van Horn, Wade D. ;
Hustedt, Eric J. ;
Schafer, Johanna M. ;
Hadziselimovic, Arina ;
Beel, Andrew J. ;
Sanders, Charles R. .
SCIENCE, 2012, 336 (6085) :1168-1171
[5]  
BAZAN NG, 1990, UPSALA J MED SCI, P97
[6]  
BLIGH EG, 1959, CAN J BIOCHEM PHYS, V37, P911
[7]   Evidence that tumor necrosis factor α converting enzyme is involved in regulated α-secretase cleavage of the Alzheimer amyloid protein precursor [J].
Buxbaum, JD ;
Liu, KN ;
Luo, YX ;
Slack, JL ;
Stocking, KL ;
Peschon, JJ ;
Johnson, RS ;
Castner, BJ ;
Cerretti, DP ;
Black, RA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (43) :27765-27767
[8]   Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model [J].
Calon, F ;
Lim, GP ;
Yang, FS ;
Morihara, T ;
Teter, B ;
Ubeda, O ;
Rostaing, P ;
Triller, A ;
Salem, N ;
Ashe, KH ;
Frautschy, SA ;
Cole, GM .
NEURON, 2004, 43 (05) :633-645
[9]   Omega-3 fatty acids and dementia [J].
Cole, Greg M. ;
Ma, Qiu-Lan ;
Frautschy, Sally A. .
PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, 2009, 81 (2-3) :213-221
[10]   Plasma and Brain Fatty Acid Profiles in Mild Cognitive Impairment and Alzheimer's Disease [J].
Cunnane, Stephen C. ;
Schneider, Julie A. ;
Tangney, Christine ;
Tremblay-Mercier, Jennifer ;
Fortier, Melanie ;
Bennett, David A. ;
Morris, Martha Clare .
JOURNAL OF ALZHEIMERS DISEASE, 2012, 29 (03) :691-697
12345678