Translating cell biology into therapeutic advances in Alzheimer's disease

被引:1480
作者
Selkoe, DJ [1 ]
机构
[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA
关键词
D O I
10.1038/399a023
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Studies of the molecular basis of Alzheimer's disease exemplify the increasingly blurred distinction between basic and applied biomedical research. The four genes so far implicated in familial Alzheimer's disease have each been shown to elevate brain levels of the self-aggregating amyloid-beta protein, leading gradually to profound neuronal and glial alteration, synaptic loss and dementia. Progress in understanding this cascade has helped to identify specific therapeutic targets and provides a model for elucidating other neurodegenerative disorders.
引用
收藏
页码:A23 / A31
页数:9
相关论文
共 100 条
[1]   Lack of apolipoprotein E dramatically reduces amyloid beta-peptide deposition [J].
Bales, KR ;
Verina, T ;
Dodel, RC ;
Du, YS ;
Altstiel, L ;
Bender, M ;
Hyslop, P ;
Johnstone, EM ;
Little, SP ;
Cummins, DJ ;
Piccardo, P ;
Ghetti, B ;
Paul, SM .
NATURE GENETICS, 1997, 17 (03) :263-264
[2]  
Baumeister R, 1997, Genes Funct, V1, P149
[3]   HYDROGEN-PEROXIDE MEDIATES AMYLOID-BETA PROTEIN TOXICITY [J].
BEHL, C ;
DAVIS, JB ;
LESLEY, R ;
SCHUBERT, D .
CELL, 1994, 77 (06) :817-827
[4]   Co-expression of beta-amyloid precursor protein (beta APP) and apolipoprotein E in cell culture: Analysis of beta APP processing [J].
Biere, AL ;
Ostaszewski, B ;
Zhao, HW ;
Gillespie, S ;
Younkin, SG ;
Selkoe, DJ .
NEUROBIOLOGY OF DISEASE, 1995, 2 (03) :177-187
[5]   A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells [J].
Black, RA ;
Rauch, CT ;
Kozlosky, CJ ;
Peschon, JJ ;
Slack, JL ;
Wolfson, MF ;
Castner, BJ ;
Stocking, KL ;
Reddy, P ;
Srinivasan, S ;
Nelson, N ;
Boiani, N ;
Schooley, KA ;
Gerhart, M ;
Davis, R ;
Fitzner, JN ;
Johnson, RS ;
Paxton, RJ ;
March, CJ ;
Cerretti, DP .
NATURE, 1997, 385 (6618) :729-733
[6]   Alpha-2 macroglobulin is genetically associated with Alzheimer disease [J].
Blacker, D ;
Wilcox, MA ;
Laird, NM ;
Rodes, L ;
Horvath, SM ;
Go, RCP ;
Perry, R ;
Watson, B ;
Bassett, SS ;
McInnis, MG ;
Albert, MS ;
Hyman, BT ;
Tanzi, RE .
NATURE GENETICS, 1998, 19 (04) :357-360
[7]   Caspase-mediated cleavage is not required for the activity of presenilins in amyloidogenesis and NOTCH signaling [J].
Brockhaus, M ;
Grünberg, J ;
Röhrig, S ;
Loetscher, H ;
Wittenburg, N ;
Baumeister, R ;
Jacobsen, H ;
Haass, C .
NEUROREPORT, 1998, 9 (07) :1481-1486
[8]   GENERATION OF BETA-AMYLOID IN THE SECRETORY PATHWAY IN NEURONAL AND NONNEURONAL CELLS [J].
BUSCIGLIO, J ;
GABUZDA, DH ;
MATSUDAIRA, P ;
YANKNER, BA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (05) :2092-2096
[9]   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
[10]   The proteolytic fragments of the Alzheimer's disease-associated presenilin-1 form heterodimers and occur as a 100-150-kDa molecular mass complex [J].
Capell, A ;
Grünberg, J ;
Pesold, B ;
Diehlmann, A ;
Citron, M ;
Nixon, R ;
Beyreuther, K ;
Selkoe, DJ ;
Haass, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (06) :3205-3211