Linking lipids to Alzheimer's disease: cholesterol and beyond

被引:728
作者
Di Paolo, Gilbert [1 ]
Kim, Tae-Wan [1 ]
机构
[1] Columbia Univ, Dept Pathol & Cell Biol, Taub Inst Res Alzheimers Dis & Aging Brain, Med Ctr, New York, NY 10032 USA
基金
美国国家卫生研究院;
关键词
AMYLOID PRECURSOR PROTEIN; GENOME-WIDE ASSOCIATION; A-BETA; GAMMA-SECRETASE; APOLIPOPROTEIN-E; MOUSE MODEL; TAU PHOSPHORYLATION; IDENTIFIES VARIANTS; COGNITIVE DEFICITS; PHOSPHOLIPASE D1;
D O I
10.1038/nrn3012
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Lipid-mediated signalling regulates a plethora of physiological processes, including crucial aspects of brain function. In addition, dysregulation of lipid pathways has been implicated in a growing number of neurodegenerative disorders, such as Alzheimer's disease (AD). Although much attention has been given to the link between cholesterol and AD pathogenesis, growing evidence suggests that other lipids, such as phosphoinositides and phosphatidic acid, have an important role. Regulators of lipid metabolism (for example, statins) are a highly successful class of marketed drugs, and exploration of lipid dysregulation in AD and identification of novel therapeutic agents acting through relevant lipid pathways offers new and effective options for the treatment of this devastating disorder.
引用
收藏
页码:284 / 296
页数:13
相关论文
共 149 条
[1]   Simvastatin Therapy Prevents Brain Trauma-Induced Increases in β-Amyloid Peptide Levels [J].
Abrahamson, Eric E. ;
Ikonomovic, Milos D. ;
Dixon, C. Edward ;
DeKosky, Steven T. .
ANNALS OF NEUROLOGY, 2009, 66 (03) :407-414
[2]   Lipid raft microdomains and neurotransmitter signalling [J].
Allen, John A. ;
Halverson-Tamboli, Robyn A. ;
Rasenick, Mark M. .
NATURE REVIEWS NEUROSCIENCE, 2007, 8 (02) :128-140
[3]   Role of ganglioside metabolism in the pathogenesis of Alzheimer's disease - a review [J].
Ariga, Toshio ;
McDonald, Michael P. ;
Yu, Robert K. .
JOURNAL OF LIPID RESEARCH, 2008, 49 (06) :1157-1175
[4]   Statins, incident Alzheimer disease, change in cognitive function, and neuropathology [J].
Arvanitakis, Z. ;
Schneider, J. A. ;
Wilson, R. S. ;
Bienias, J. L. ;
Kelly, J. F. ;
Evans, D. A. ;
Bennett, D. A. .
NEUROLOGY, 2008, 70 (19) :1795-1802
[5]   Tau-mediated neurodegeneration in Alzheimer's disease and related disorders [J].
Ballatore, Carlo ;
Lee, Virginia M. -Y. ;
Trojanowski, John Q. .
NATURE REVIEWS NEUROSCIENCE, 2007, 8 (09) :663-672
[6]   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
[7]   Oligomeric amyloid-β peptide disrupts phosphatidylinositol-4,5-bisphosphate metabolism [J].
Berman, Diego E. ;
Dall'Armi, Claudia ;
Voronov, Sergey V. ;
McIntire, Laura Beth J. ;
Zhang, Hong ;
Moore, Ann Z. ;
Staniszewski, Agniezka ;
Arancio, Ottavio ;
Kim, Tae-Wan ;
Di Paolo, Gilbert .
NATURE NEUROSCIENCE, 2008, 11 (05) :547-554
[8]   Elimination of GD3 synthase improves memory and reduces amyloid-β plaque load in transgenic mice [J].
Bernardo, Alexandra ;
Harrison, Fiona E. ;
McCord, Meghan ;
Zhao, Jiali ;
Bruchey, Aleksandra ;
Davies, Sean S. ;
Roberts, L. Jackson, II ;
Mathews, Paul M. ;
Matsuoka, Yasuji ;
Ariga, Toshio ;
Yu, Robert K. ;
Thompson, Rebecca ;
McDonald, Michael P. .
NEUROBIOLOGY OF AGING, 2009, 30 (11) :1777-1791
[9]   Thirty years of Alzheimer's disease genetics: the implications of systematic meta-analyses [J].
Bertram, Lars ;
Tanzi, Rudolph E. .
NATURE REVIEWS NEUROSCIENCE, 2008, 9 (10) :768-778
[10]   Genome-wide association studies in Alzheimer's disease [J].
Bertram, Lars ;
Tanzi, Rudolph E. .
HUMAN MOLECULAR GENETICS, 2009, 18 :R137-R145