AMYLOID-BETA PROTEIN-INDUCED NEURONAL CELL-DEATH - NEUROTOXIC PROPERTIES OF AGGREGATED AMYLOID-BETA PROTEIN

被引:117
作者
UEDA, K
FUKUI, Y
KAGEYAMA, H
机构
[1] Division of Pharmacology, Shionogi Research Laboratories, Shionogi and Co. Ltd., Toyonaka, 561
关键词
ALZHEIMERS DISEASE; AMYLOID-BETA PROTEIN; AGGREGATION; NEUROTOXIC; HIPPOCAMPAL CELL CULTURE; MTT ASSAY;
D O I
10.1016/0006-8993(94)91736-1
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The neurotoxic effects of soluble and aggregated synthetic amyloid beta protein (AbetaP) have been investigated in rat primary cultures. Freshly solubilized beta(1-40) was neurotoxic not to immature, but to mature hippocampal neurons. On the other hand, aggregated beta(1-40) was neurotoxic to both. Neurotoxicity induced by aggregated beta(1-40) was 10-fold more potent than soluble beta(1-40) and was not prevented by substance P. The neurotoxicity of aggregated beta(1-40) to cultured neurons depended on the peptide concentration and the duration of exposure to, it. Cerebral cortical and hippocampal neurons were significantly susceptible to aggregated beta(1-40) than cerebellar granular cells, and cultured astrocytes were not vulnerable to aggregated beta(1-40) even at high concentrations.
引用
收藏
页码:240 / 244
页数:5
相关论文
共 23 条
[11]   INABILITY OF BETA-AMYLOID (25-35) TO BIND TO CENTRAL-NERVOUS-SYSTEM NEUROKININ-1 RECEPTORS [J].
LEE, JM ;
WEINSTEIN, DA ;
KOWALL, NW ;
BEAL, MF .
DRUG DEVELOPMENT RESEARCH, 1992, 27 (04) :441-444
[12]   AN AUTOMATED COLORIMETRIC MICROASSAY FOR NEURONOTROPHIC FACTORS [J].
MANTHORPE, M ;
FAGNANI, R ;
SKAPER, SD ;
VARON, S .
DEVELOPMENTAL BRAIN RESEARCH, 1986, 25 (02) :191-198
[13]   BETA-AMYLOID PEPTIDES DESTABILIZE CALCIUM HOMEOSTASIS AND RENDER HUMAN CORTICAL-NEURONS VULNERABLE TO EXCITOTOXICITY [J].
MATTSON, MP ;
CHENG, B ;
DAVIS, D ;
BRYANT, K ;
LIEBERBURG, I ;
RYDEL, RE .
JOURNAL OF NEUROSCIENCE, 1992, 12 (02) :376-389
[14]   BETA-AMYLOID PRECURSOR PROTEIN AND ALZHEIMERS-DISEASE - THE PEPTIDE PLOT THICKENS [J].
MATTSON, MP ;
RYDEL, RE .
NEUROBIOLOGY OF AGING, 1992, 13 (05) :617-621
[15]   AGGREGATION-RELATED TOXICITY OF SYNTHETIC BETA-AMYLOID PROTEIN IN HIPPOCAMPAL CULTURES [J].
PIKE, CJ ;
WALENCEWICZ, AJ ;
GLABE, CG ;
COTMAN, CW .
EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION, 1991, 207 (04) :367-368
[16]  
PIKE CJ, 1991, BRAIN RES, V563, P279
[17]   RECEPTOR-MEDIATED SPECIFIC BIOLOGICAL-ACTIVITY OF A BETA-AMYLOID PROTEIN-FRAGMENT FOR NK-1 SUBSTANCE-P RECEPTORS [J].
SHIMOHIGASHI, Y ;
MATSUMOTO, H ;
TAKANO, Y ;
SAITO, R ;
IWATA, T ;
KAMIYA, H ;
OHNO, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1993, 193 (02) :624-630
[18]  
STEFANO MD, 1993, BRAIN RES, V600, P166
[19]  
WHISTON JS, 1990, NEUROSCI LETT, V110, P319
[20]  
WHISTON JS, 1989, SCIENCE, V243, P1488