Identification of the major Aβ1-42-degrading catabolic pathway in brain parenchyma:: Suppression leads to biochemical and pathological deposition
Identification of the major Aβ1-42-degrading catabolic pathway in brain parenchyma:: Suppression leads to biochemical and pathological deposition
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DOI：
10.1038/72237
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发表时间：
2000-02-01
期刊：
影响因子：
82.9
通讯作者：
Saido, TC
中科院分区：
文献类型：
--
作者：
Iwata, N;Tsubuki, S;Saido, TC
阿尔茨海默病淀粉样β肽（A β）是一种在正常条件下不断合成代谢和分解代谢的生理肽。本研究通过对大鼠海马注射多放射性标记的合成肽进行示踪研究，探讨了卡他汀的作用机制。A β（1-42）肽通过中性内肽酶（NEP）进行的有限蛋白水解完全降解，该酶与生化分析的脑啡肽酶相似或相同。一致地，NEP抑制剂输注导致脑中内源性A β（42）的生化和病理沉积。因此，这种NEP催化的蛋白水解限制了A β（42）催化剂的速率，其上调可以通过防止A β积累来降低发展阿尔茨海默病的风险。
Alzheimer amyloid beta-peptide (A beta) is a physiological peptide constantly anabolized and catabolized under normal conditions. We investigated the mechanism of catabolism by tracing multiple-radiolabeled synthetic peptide injected into rat hippocampus. The A beta(1-42) peptide underwent full degradation through limited proteolysis conducted by neutral endopeptidase (NEP) similar or identical to neprilysin as biochemically analyzed. Consistently, NEP inhibitor infusion resulted in both biochemical and pathological deposition of endogenous A beta(42) in brain. This NEP-catalyzed proteolysis therefore limits the rate of A beta(42) catabolism, up-regulation of which could reduce the risk of developing Alzheimer's disease by preventing A beta accumulation.