Pyroglutamate Amyloid-β (Aβ): A Hatchet Man in Alzheimer Disease

被引:183
作者
Jawhar, Sadim [1 ]
Wirths, Oliver [1 ]
Bayer, Thomas A. [1 ]
机构
[1] Univ Gottingen, Dept Mol Psychiat, Univ Med Gottingen, D-37075 Gottingen, Germany
关键词
HUMAN GLUTAMINYL CYCLASE; TRANSGENIC MOUSE MODEL; PLAQUE CORE PROTEIN; PEPTIDES IN-VITRO; SENILE PLAQUE; DOWNS-SYNDROME; BIOLOGICAL SIGNIFICANCE; PRECURSOR PROTEIN; MAJOR COMPONENT; SYNDROME BRAINS;
D O I
10.1074/jbc.R111.288308
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pyroglutamate-modified amyloid-beta (A beta(pE3)) peptides are gaining considerable attention as potential key participants in the pathology of Alzheimer disease (AD) due to their abundance in AD brain, high aggregation propensity, stability, and cellular toxicity. Transgenic mice that produce high levels of A beta(pE3-42) show severe neuron loss. Recent in vitro and in vivo experiments have proven that the enzyme glutaminyl cyclase catalyzes the formation of A beta(pE3).In this minireview, we summarize the current knowledge on A beta(pE3), discussing its discovery, biochemical properties, molecular events determining formation, prevalence in the brains of AD patients, Alzheimer mouse models, and potential as a target for therapy and as a diagnostic marker.
引用
收藏
页码:38825 / 38832
页数:8
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