Unaltered secretion of beta-amyloid precursor protein in gelatinase a (matrix metalloproteinase 2)-deficient mice

被引:293
作者
Itoh, T
Ikeda, T
Gomi, H
Nakao, S
Suzuki, T
Itohara, S
机构
[1] KYOTO UNIV,INST VIRUS RES,SAKYO KU,KYOTO 60601,JAPAN
[2] UNIV TOKYO,FAC PHARMACEUT SCI,BUNKYO KU,TOKYO 113,JAPAN
关键词
D O I
10.1074/jbc.272.36.22389
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
The beta-amyloid peptide, which forms extracellular cerebral deposits in Alzheimer's disease, is derived from a large membrane-spanning glycoprotein referred to as the beta-amyloid precursor protein (APP). The APP is normally cleaved within the beta-amyloid region by a putative proteinase (alpha-secretase) to generate large soluble amino-terminal derivatives of APP, and this event pre vents the beta-amyloid peptide formation. It has been suggested that the gelatinase A (matrix metalloproteinase 2, a 72-kDa type IV collagenase) may act either as alpha-secretase or as beta-secretase. Mice devoid of gelatinase A generated by gene targeting develop normally, except for a subtle delay in their growth, thus providing a useful system to examine the role of gelatinase A in the cleavage and secretion of APP in vivo. We show here that APP is cleaved within the beta-amyloid region and secreted into the extracellular milieu of brain and cultured fibroblasts without gelatinase A activity. The data suggest that gelatinase A does not play an essential role in the generation and release of soluble derivatives of APP at physiological conditions.
引用
收藏
页码:22389 / 22392
页数:4
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