β-amyloid catabolism:: roles for neprilysin (NEP) and other metallopeptidases?
β-amyloid catabolism:: roles for neprilysin (NEP) and other metallopeptidases?
复制标题
DOI：
10.1046/j.1471-4159.2002.00855.x
复制
发表时间：
2002-04-01
影响因子：
4.7
通讯作者：
Turner, AJ
中科院分区：
文献类型：
--
作者：
Carson, JA;Turner, AJ
淀粉样蛋白β -肽（Abeta）的稳态水平代表了其通过β和γ分泌酶的作用从淀粉样蛋白前体蛋白（APP）生物合成与多种蛋白水解酶的分解代谢之间的平衡。近年来，人们关注的焦点集中在淀粉样蛋白代谢中的锌金属蛋白酶NEP家族成员。NEP本身在体外和体内降解Abeta（1-40）和Abeta(1-42)， NEP抑制剂可以阻止这种代谢。其他NEP家族成员，如内皮素转换酶，可能有助于淀粉样蛋白分解代谢，也可能在神经保护中发挥作用。另一种金属蛋白酶，胰岛素（胰岛素降解酶）也被认为是淀粉样蛋白降解酶，可能更广泛地参与淀粉样蛋白形成肽的代谢。其他候选酶包括血管紧张素转换酶、一些基质金属蛋白酶、纤溶酶和间接的硫寡肽酶（内肽酶-24.15）。这篇综述批判性地评估了与淀粉样蛋白分解代谢相关的蛋白酶的证据。旨在促进β降解的治疗策略可能为阿尔茨海默病的治疗提供新的途径。
The steady-state level of amyloid beta-peptide (Abeta) represents a balance between its biosynthesis from the amyloid precursor protein (APP) through the action of the beta- and gamma-secretases and its catabolism by a variety of proteolytic enzymes. Recent attention has focused on members of the neprilysin (NEP) family of zinc metalloproteinases in amyloid metabolism. NEP itself degrades both Abeta(1-40) and Abeta(1-42) in vitro and in vivo, and this metabolism is prevented by NEP inhibitors. Other NEP family members, for example endothelin-converting enzyme, may contribute to amyloid catabolism and may also play a role in neuroprotection. Another metalloproteinase, insulysin (insulin-degrading enzyme) has also been advocated as an amyloid-degrading enzyme and may contribute more generally to metabolism of amyloid-forming peptides. Other candidate enzymes proposed include angiotensin-converting enzyme, some matrix metalloproteinases, plasmin and, indirectly, thimet oligopeptidase (endopeptidase-24.15). This review critically evaluates the evidence relating to proteinases implicated in amyloid catabolism. Therapeutic strategies aimed at promoting Abeta degradation may provide a novel approach to the therapy of Alzheimer's disease.