Changes with Age in the Activities of β-Secretase and the Aβ-Degrading Enzymes Neprilysin, Insulin-Degrading Enzyme and Angiotensin-Converting Enzyme
Changes with Age in the Activities of β-Secretase and the Aβ-Degrading Enzymes Neprilysin, Insulin-Degrading Enzyme and Angiotensin-Converting Enzyme
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DOI：
10.1111/j.1750-3639.2010.00375.x
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发表时间：
2010-07-01
期刊：
影响因子：
6.4
通讯作者：
Love, Seth
中科院分区：
文献类型：
--
作者：
Miners, J. Scott;van Helmond, Zoe;Love, Seth
我们最近发现，在正常的大脑中，不溶性A增加，而可溶性A随着年龄的增长而减少。我们现在报道了β -分泌酶（BACE-1）和A - β降解酶的活性随年龄的变化，以及它们与可溶性和不可溶性A - β浓度的关系。我们测量了正常对照脑（16 -95岁）的BACE-1活性以及NEP、胰岛素降解酶（IDE）和血管紧张素转换酶（ACE）水平和活性。我们还将测量结果与AD患者进行了比较。在对照组中，BACE-1活性与年龄密切相关，而在AD患者中则明显升高。在对照组中，NEP和IDE活性（而不是蛋白质水平）随着年龄的增长而增加，而ACE活性和水平则没有增加。BACE-1活性与不溶性A β呈正相关，与可溶性A β呈负相关。IDE活性与不溶性A β直接相关，NEP活性与可溶性A β负相关。ACE水平与对照组不溶性A β呈正相关，与可溶性A β呈负相关，与AD无相关性。A -合成酶和A -降解酶的活性都随着年龄的增长而增加，与可溶性A -下降和不溶性A -增加相一致。需要进一步的研究来确定这些酶活性和A -水平的变化是否有因果关系，如果有因果关系，如何有因果关系。
We recently found that insoluble A beta increases, but soluble A beta decreases with age in normal brains. We now report the changes in activities of beta-secretase (BACE-1) and A beta-degrading enzymes with age, and their relationships to concentrations of soluble and insoluble A beta. We measured BACE-1 activity and the levels and activities of neprilysin (NEP), insulin-degrading enzyme (IDE) and angiotensin-converting enzyme (ACE) in normal control brains (16 years-95 years). We also compared the measurements to those in AD. BACE-1 activity correlated closely with age in controls and was significantly higher in AD. In controls, NEP and IDE activities (but not protein levels) increased with age but ACE activity and level did not. BACE-1 activity correlated directly with insoluble but inversely with soluble A beta. IDE activity correlated directly with insoluble A beta and NEP activity was inversely related to soluble A beta. ACE level correlated directly with insoluble and inversely with soluble A beta in controls but not AD. Both A beta-synthesizing and -degrading enzyme activities increase with age, coinciding with declining soluble A beta and increasing insoluble A beta. Further research is needed to establish whether these changes in enzyme activity and A beta levels are causally related and if so how.