GLYCATED TAU-PROTEIN IN ALZHEIMER-DISEASE - A MECHANISM FOR INDUCTION OF OXIDANT STRESS

被引:509
作者
YAN, SD
CHEN, X
SCHMIDT, AM
BRETT, J
GODMAN, G
ZOU, YS
SCOTT, CW
CAPUTO, C
FRAPPIER, T
SMITH, MA
PERRY, G
YEN, SH
STERN, D
机构
[1] COLUMBIA UNIV,COLL PHYS & SURG,DEPT CELLULAR BIOPHYS,NEW YORK,NY 10032
[2] COLUMBIA UNIV,COLL PHYS & SURG,DEPT NEUROL,NEW YORK,NY 10032
[3] COLUMBIA UNIV,COLL PHYS & SURG,DEPT PATHOL,NEW YORK,NY 10032
[4] ICI AMER INC,ICI PHARMACEUT GRP,WILMINGTON,DE 19897
[5] CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106
[6] ALBERT EINSTEIN COLL MED,DEPT PATHOL,NEW YORK,NY 10461
关键词
GLYCATION; REACTIVE OXYGEN INTERMEDIATE; NEURON;
D O I
10.1073/pnas.91.16.7787
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 stability of proteins that constitute the neurofibrillary tangles and senile plaques of Alzheimer disease suggests that they would be ideal substrates for nonenzymatic glycation, a process that occurs over long times, even at normal levels of glucose, ultimately resulting in the formation of advanced glycation end products (AGEs). AGE-modified proteins aggregate, and they generate reactive oxygen intermediates. Using monospecific antibody to AGEs, we have colocalized these AGEs with paired helical filament tau in neurofibrillary tangles in sporadic Alzheimer disease. Such neurons also exhibited evidence of oxidant stress: induction of malondialdehyde epitopes and heme oxygenase 1 antigen. AGE-recombinant tau generated reactive oxygen intermediates and, when introduced into the cytoplasm of SH-SY5Y neuroblastoma cells, induced oxidant stress. We propose that in Alzheimer disease, AGEs in paired helical filament tau can induce oxidant stress, thereby promoting neuronal dysfunction.
引用
收藏
页码:7787 / 7791
页数:5
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