Genetic and molecular aspects of Alzheimer's disease shed light on new mechanisms of transcriptional regulation

被引：61
作者：
Marambaud, P
Robakis, NK
机构：
[1] CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA
[2] CUNY Mt Sinai Sch Med, Fishberg Res Ctr Neurobiol, New York, NY 10029 USA
来源：
GENES BRAIN AND BEHAVIOR | 2005年 / 4卷 / 03期
关键词：
Alzheimer's disease; APP; cadherins; gamma-secretase; notch; presenilins;
D O I：
10.1111/j.1601-183X.2005.00086.x
中图分类号：
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号：
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要：
Rapid advances made in biological research aimed at understanding the molecular basis of the pathogenesis of Alzheimer's disease have led to the characterization of a novel catalytic activity termed gamma-secretase. First described for its P-amyloid-producing function, gamma-secretase is now actively studied for its role in a novel signal transduction paradigm, which implicates cell-surface receptor proteolysis and direct surf ace-to-nucleus signal transduction. gamma-Secretase targets numerous type I protein receptors involved in diverse functions ranging from normal development to neurodegeneration. In this Review we discuss how the study of the genetic and molecular aspects of Alzheimer's disease has revealed a dual role of gamma-secretase in transcriptional regulation and in the pathogenesis of familial Alzheimer's disease.
引用
收藏
页码：134 / 146
页数：13
相关论文
共 180 条
[71]   Identity and function of γ-secretase [J].
Kimberly, WT ;
Wolfe, MS .
JOURNAL OF NEUROSCIENCE RESEARCH, 2003, 74 (03) :353-360
[72]   The transmembrane aspartates in presenilin 1 and 2 are obligatory for γ-secretase activity and amyloid β-protein generation [J].
Kimberly, WT ;
Xia, WM ;
Rahmati, T ;
Wolfe, MS ;
Selkoe, DJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (05) :3173-3178
[73]   Targeting small Aβ oligomers:: the solution to an Alzheimer's disease conundrum? [J].
Klein, WL ;
Krafft, GA ;
Finch, CE .
TRENDS IN NEUROSCIENCES, 2001, 24 (04) :219-224
[74]   Alzheimer-associated presenilins 1 and 2: Neuronal expression in brain and localization to intracellular membranes in mammalian cells [J].
Kovacs, DM ;
Fausett, HJ ;
Page, KJ ;
Kim, TW ;
Moir, RD ;
Merriam, DE ;
Hollister, RD ;
Hallmark, OG ;
Mancini, R ;
Felsenstein, KM ;
Hyman, BT ;
Tanzi, RE ;
Wasco, W .
NATURE MEDICINE, 1996, 2 (02) :224-229
[75]   Presenilin-dependent intramembrane proteolysis of CD44 leads to the liberation of its intracellular domain and the secretion of an Aβ-like peptide [J].
Lammich, S ;
Okochi, M ;
Takeda, M ;
Kaether, C ;
Capell, A ;
Zimmer, AK ;
Edbauer, D ;
Walter, J ;
Steiner, H ;
Haass, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (47) :44754-44759
[76]   Constitutive and regulated α-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease [J].
Lammich, S ;
Kojro, E ;
Postina, R ;
Gilbert, S ;
Pfeiffer, R ;
Jasionowski, M ;
Haass, C ;
Fahrenholz, F .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (07) :3922-3927
[77]   Assembly of the γ-secretase complex involves early formation of an intermediate subcomplex of Aph-1 and nicastrin [J].
LaVoie, MJ ;
Fraering, PC ;
Ostaszewski, BL ;
Ye, WJ ;
Kimberly, WT ;
Wolfe, MS ;
Selkoe, DJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (39) :37213-37222
[78]   The Notch ligands, Jagged and Delta, are sequentially processed by α-secretase and presenilin/γ-secretase and release signaling fragments [J].
LaVoie, MJ ;
Selkoe, DJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (36) :34427-34437
[79]   Presenilin-dependent γ-secretase-like intramembrane cleavage of ErbB4 [J].
Lee, HJ ;
Jung, KM ;
Huang, YZ ;
Bennett, LB ;
Lee, JS ;
Mei, L ;
Kim, TW .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (08) :6318-6323
[80]   Assessment of normal and mutant human presenilin function in Caenorhabditis elegans [J].
Levitan, D ;
Doyle, TG ;
Brousseau, D ;
Lee, MK ;
Thinakaran, G ;
Slunt, HH ;
Sisodia, SS ;
Greenwald, I .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (25) :14940-14944
3456789101112