PRODUCTION OF THE ALZHEIMER AMYLOID-BETA PROTEIN BY NORMAL PROTEOLYTIC PROCESSING

被引:1377
作者
SHOJI, M
GOLDE, TE
GHISO, J
CHEUNG, TT
ESTUS, S
SHAFFER, LM
CAI, XD
MCKAY, DM
TINTNER, R
FRANGIONE, B
YOUNKIN, SG
机构
[1] CASE WESTERN RESERVE UNIV,INST PATHOL,DIV NEUROPATHOL,CLEVELAND,OH 44106
[2] UNIV TEXAS,SW MED CTR,DEPT NEUROL,DALLAS,TX 75235
[3] UNIV TEXAS,SW MED CTR,ALZHEIMERS DIS RES CTR,DALLAS,TX 75235
[4] GUNMA UNIV,DEPT NEUROL,MAEBASHI,GUNMA 371,JAPAN
[5] NYU MED CTR,DEPT PATHOL,NEW YORK,NY 10016
[6] WASHINGTON UNIV,SCH MED,DEPT MOLEC BIOL & PHARMACOL,ST LOUIS,MO 63110
关键词
D O I
10.1126/science.1439760
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
The 4-kilodalton (39 to 43 amino acids) amyloid beta protein (betaAP), which is deposited as amyloid in the brains of patients with Alzheimer's disease, is derived from a large protein, the amyloid beta protein precursor (betaAPP). Human mononuclear leukemic (K562) cells expressing a betaAP-bearing, carboxyl-terminal betaAPP derivative released significant amounts of a soluble 4-kilodalton betaAPP derivative essentially identical to the betaAP deposited in Alzheimer's disease. Human neuroblastoma (M17) cells transfected with constructs expressing full-length betaAPP and M17 cells expressing only endogenous betaAPP also released soluble 4-kilodalton betaAP, and a similar, if not identical, fragment was readily detected in cerebrospinal fluid from individuals with Alzheimer's disease and normal individuals. Thus cells normally produce and release soluble 4-kilodalton betaAP that is essentially identical to the 4-kilodalton betaAP deposited as insoluble amyloid fibrils in Alzheimer's disease.
引用
收藏
页码:126 / 129
页数:4
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