Presenilins in memory, Alzheimer's disease, and therapy

被引:49
作者
Marjaux, E [1 ]
Hartmann, D [1 ]
De Strooper, B [1 ]
机构
[1] Katholieke Univ Leuven, UZ Gasthuisberg, Ctr Human Genet, Lab Neuronal Cell Biol & Gene Transfer, B-3000 Louvain, Belgium
关键词
D O I
10.1016/S0896-6273(04)00218-1
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Presenilins are considered to be the catalytic subunits of the gamma-secretase complex and are therefore drug targets for Alzheimer's disease. They are also essential for the fine tuning of the immunological system and for memory and synaptic plasticity. Genetic ablation in the forebrain results in a progressive neurodegenerative process that is independent from Abeta generation. The question arises as to what extent these observations should influence our thinking on the pathogenesis of Alzheimer's disease and on strategies to further develop gamma-secretase inhibitors.
引用
收藏
页码:189 / 192
页数:4
相关论文
共 21 条
[1]   Aph-1, Pen-2, and nicastrin with presenilin generate an active γ-secretase complex [J].
De Strooper, B .
NEURON, 2003, 38 (01) :9-12
[2]   Mice lacking both presenilin genes exhibit early embryonic patterning defects [J].
Donoviel, DB ;
Hadjantonakis, AK ;
Ikeda, M ;
Zheng, H ;
Hyslop, PS ;
Bernstein, A .
GENES & DEVELOPMENT, 1999, 13 (21) :2801-2810
[3]   Deficient neurogenesis in forebrain-specific presenilin-1 knockout mice is associated with reduced clearance of hippocampal memory traces [J].
Feng, RB ;
Rampon, C ;
Tang, YP ;
Shrom, D ;
Jin, J ;
Kim, M ;
Sopher, B ;
Martin, GM ;
Kim, SH ;
Langdon, RB ;
Sisodia, SS ;
Tsien, JZ .
NEURON, 2001, 32 (05) :911-926
[4]  
Handler M, 2000, DEVELOPMENT, V127, P2593
[5]   Presenilin-1 deficiency leads to loss of Cajal-Retzius neurons and cortical dysplasia similar to human type 2 lissencephaly [J].
Hartmann, D ;
De Strooper, B ;
Saftig, P .
CURRENT BIOLOGY, 1999, 9 (14) :719-727
[6]   Presenilin 2 deficiency causes a mild pulmonary phenotype and no changes in amyloid precursor protein processing but enhances the embryonic lethal phenotype of presenilin 1 deficiency [J].
Herreman, A ;
Hartmann, D ;
Annaert, W ;
Saftig, P ;
Craessaerts, K ;
Serneels, L ;
Umans, L ;
Schrijvers, V ;
Checler, F ;
Vanderstichele, H ;
Baekelandt, V ;
Dressel, R ;
Cupers, P ;
Huylebroeck, D ;
Zwijsen, A ;
Van Leuven, F ;
De Strooper, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (21) :11872-11877
[7]  
KOPAN R, 2004, IN PRESS NAT REV CEL
[8]   Abnormal blood vessel development in mice lacking presenilin-1 [J].
Nakajima, M ;
Yuasa, S ;
Ueno, M ;
Takakura, N ;
Koseki, H ;
Shirasawa, T .
MECHANISMS OF DEVELOPMENT, 2003, 120 (06) :657-667
[9]   Notch1 functions as a tumor suppressor in mouse skin [J].
Nicolas, M ;
Wolfer, A ;
Raj, K ;
Kummer, JA ;
Mill, P ;
van Noort, M ;
Hui, CC ;
Clevers, H ;
Dotto, GP ;
Radtke, F .
NATURE GENETICS, 2003, 33 (03) :416-421
[10]   Presenilins mutated at Asp-257 or Asp-385 restore Pen-2 expression and nicastrin glycosylation but remain catalytically inactive in the absence of wild type presenilin [J].
Nyabi, O ;
Bentahir, M ;
Horré, K ;
Herreman, A ;
Gottardi-Littell, N ;
Van Broeckhoven, C ;
Merchiers, P ;
Spittaels, K ;
Annaert, W ;
De Strooper, B .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (44) :43430-43436