期刊
BIOCHEMICAL SOCIETY TRANSACTIONS
卷 35, 期 -, 页码 571-573出版社
PORTLAND PRESS LTD
DOI: 10.1042/BST0350571
关键词
Alzheimer's disease; amyloid; beta-site amyloid precursor pnotein-cleaving enzyme 1 (BACE 1); aspartic proteinase; copper; proteinase
The amyloidogenic processing pathway of the APP (amyloid precursor protein) generates A beta (amyloid peptide), the major constituent in Alzheimer's disease senile plaques. This processing is catalysed by two unusual membrane-localized aspartic proteinases, beta-secretase [BACE1 (beta-site APP-cleaving enzyme 1)] and the gamma-secretase complex. There is a clear link between APP processing and copper homoeostasis in the brain. APP binds copper and zinc in the extracellular domain and A beta also binds copper, zinc and iron. we have found that a 24-residue peptide corresponding to the C-terminal domain of BACE1 binds a single copper(l) atom with high affinity through cysteine residues. We also observed that the cytoplasmic domain of BACE1 interacts with CCS, the dedicated copper chaperone for SOD1 (superoxide dismutase 1). overproduction of BACE1 reduces SOD1 activity in cells. Consequently, SOD1 activity, cytosolic copper and ectodomain cleavage of APP are linked through BACE1.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据