BACE (beta-secretase) modulates the processing of APLP2 in vivo.
BACE (beta-secretase) modulates the processing of APLP2 in vivo.
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发表时间：
2004
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通讯作者：
L. Pastorino;A. Ikin;S. Lamprianou;N. Vacaresse;J. Revelli;K. Platt;P. Paganetti;P. Mathews;
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作者：
L. Pastorino;A. Ikin;S. Lamprianou;N. Vacaresse;J. Revelli;K. Platt;P. Paganetti;P. Mathews;
BACE 是一种天冬氨酰蛋白酶，可在 β-分泌酶切割位点切割淀粉样前体蛋白 (APP)，并与阿尔茨海默病有关。我们研究的目的是确定 BACE 是否影响 APP 同源物 APLP2 的加工。为此，我们开发了 BACE 基因敲除小鼠，并定向插入 β-半乳糖苷酶基因。通过差异染色确定，BACE 似乎只在神经元中表达。 BACE 在皮质、海马、小脑、脑桥和脊髓的特定区域表达。 BACE 敲除中 APP 处理发生改变，Abeta 水平降低。 BACE KO 小鼠中 APLP2 蛋白水解产物的水平降低，但 BACE 转基因小鼠中 APLP2 蛋白水解产物的水平升高。 BACE 在培养细胞中的过度表达导致 APLP2 加工增加。我们的结果强烈表明 BACE 是一种调节 APP 和 APLP2 加工的神经元蛋白。
BACE is an aspartyl protease that cleaves the amyloid precursor protein (APP) at the beta-secretase cleavage site and is involved in Alzheimer's disease. The aim of our study was to determine whether BACE affects the processing of the APP homolog APLP2. To this end, we developed BACE knockout mice with a targeted insertion of the gene for beta-galactosidase. BACE appeared to be exclusively expressed in neurons as determined by differential staining. BACE was expressed in specific areas in the cortex, hippocampus, cerebellum, pons, and spinal cord. APP processing was altered in the BACE knockouts with Abeta levels decreasing. The levels of APLP2 proteolytic products were decreased in BACE KO mice, but increased in BACE transgenic mice. Overexpression of BACE in cultured cells led to increased APLP2 processing. Our results strongly suggest that BACE is a neuronal protein that modulates the processing of both APP and APLP2.