AMYLOID-BETA PEPTIDE INDUCES CYTOPLASMIC ACCUMULATION OF AMYLOID PROTEIN-PRECURSOR VIA TAU-PROTEIN KINASE-I GLYCOGEN-SYNTHASE KINASE-3-BETA IN RAT HIPPOCAMPAL-NEURONS

被引：58

作者：

TAKASHIMA, A ^{[1
]}

YAMAGUCHI, H ^{[1
]}

NOGUCHI, K ^{[1
]}

MICHEL, G ^{[1
]}

ISHIGURO, K ^{[1
]}

SATO, K ^{[1
]}

HOSHINO, T ^{[1
]}

HOSHI, M ^{[1
]}

IMAHORI, K ^{[1
]}

机构：

[1] GUNMA UNIV, COLL MED CARE & TECHNOL, MAEBASHI, GUMMA 371, JAPAN

来源：

NEUROSCIENCE LETTERS | 1995年 / 198卷 / 02期

关键词：

AMYLOID BETA PROTEIN; AMYLOID PROTEIN PRECURSOR; ALZHEIMERS; NEUROFIBRILLARY TANGLES; PAIRED HELICAL FILAMENTS; TAU PROTEIN KINASE I GLYCOGEN SYNTHASE KINASE-3-BETA;

D O I：

10.1016/0304-3940(95)11964-X

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Exogenous application of synthetic amyloid beta protein (A beta) is known to induce neurotoxic effects in rat hippocampal culture. We report here that A beta (25-35) induces accumulation of amyloid precursor protein (APP) derivatives in the cytoplasm of neurons. At the same time, the level of the secreted form of APP released into the culture medium decreases. Tau protein kinase I/glycogen synthase kinase-3 beta (TPK I/GSK-3 beta) antisense oligonucleotide blocked APP accumulation and prevented neuronal death. These results provide evidence that APP accumulation after A beta treatment is regulated by TPK I/GSK-3 beta. A beta neurotoxicity is probably mediated via phosphorylation of tau by TPK I/GSK-3 beta, resulting in an impairment of axonal transport, and cytoplasmic accumulation of APP.

引用

页码：83 / 86

页数：4

共 22 条

[1]

ANDERSON AJ, 1993, SOC NEUROSCI, V19, P1252

[2] VITAMIN-E PROTECTS NERVE-CELLS FROM AMYLOID BETA-PROTEIN TOXICITY [J].

BEHL, C ;

DAVIS, J ;

COLE, GM ;

SCHUBERT, D .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1992, 186 (02) :944-950

[3] HYDROGEN-PEROXIDE MEDIATES AMYLOID-BETA PROTEIN TOXICITY [J].

BEHL, C ;

DAVIS, JB ;

LESLEY, R ;

SCHUBERT, D .

CELL, 1994, 77 (06) :817-827

[4] AGGREGATION OF THE AMYLOID PRECURSOR PROTEIN WITHIN DEGENERATING NEURONS AND DYSTROPHIC NEURITES IN ALZHEIMERS-DISEASE [J].

CUMMINGS, BJ ;

SU, JH ;

GEDDES, JW ;

VANNOSTRAND, WE ;

WAGNER, SL ;

CUNNINGHAM, DD ;

COTMAN, CW .

NEUROSCIENCE, 1992, 48 (04) :763-777

[5]

FERREIRA A, 1993, J NEUROSCI, V13, P3112

[6] SECRETED FORMS OF BETA-AMYLOID PRECURSOR PROTEIN PROTECT HIPPOCAMPAL-NEURONS AGAINST AMYLOID BETA-PEPTIDE-INDUCED OXIDATIVE INJURY [J].

GOODMAN, Y ;

MATTSON, MP .

EXPERIMENTAL NEUROLOGY, 1994, 128 (01) :1-12

[7] ALZHEIMERS-DISEASE - THE AMYLOID CASCADE HYPOTHESIS [J].

HARDY, JA ;

HIGGINS, GA .

SCIENCE, 1992, 256 (5054) :184-185

[8] PHOSPHORYLATION SITES ON TAU BY TAU PROTEIN KINASE-I, A BOVINE DERIVED KINASE GENERATING AN EPITOPE OF PAIRED HELICAL FILAMENTS [J].

ISHIGURO, K ;

OMORI, A ;

TAKAMATSU, M ;

SATO, K ;

ARIOKA, M ;

UCHIDA, T ;

IMAHORI, K .

NEUROSCIENCE LETTERS, 1992, 148 (1-2) :202-206

[9]

KOO EH, 1990, P NATL ACAD SCI USA, V13, P3136

[10] 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

← 1 2 3 →