阿尔茨海默病中APP介导的氧化应激的可能机制。

Possible mechanisms of APP-mediated oxidative stress in Alzheimer's disease.

作者信息

Multhaup Gerd, Scheuermann Stefan, Schlicksupp Andrea, Simons Andreas, Strauss Markus, Kemmling André, Oehler Christian, Cappai Roberto, Pipkorn Rüdiger, Bayer Thomas A

机构信息

ZMBH--Center for Molecular Biology, University of Heidelberg, Heidelberg, Germany.

出版信息

Free Radic Biol Med. 2002 Jul 1;33(1):45-51. doi: 10.1016/s0891-5849(02)00806-7.

DOI:10.1016/s0891-5849(02)00806-7

PMID:12086681

Abstract

Oxidative stress was presented to play an important role in the pathogenesis of Alzheimer's disease (AD), especially in the early evolution of AD amyloidogenesis and not only as a consequence thereof. The effect of oxidative stress catalysed by transition metals appears to have a critical relevance in AD. Metal-ion homeostasis is severely dysregulated in AD and it was found that experimentally induced disturbances in the homeostasis of Zn(II) and Cu(II) affect the amyloid precursor protein (APP) metabolism. APP itself binds Zn(II) and Cu(II) at nanomolar concentrations and an altered APP metabolism or expression level is believed to result in neurotoxic processes.

摘要

氧化应激在阿尔茨海默病（AD）的发病机制中起着重要作用，尤其是在AD淀粉样蛋白生成的早期演变过程中，而不仅仅是其结果。过渡金属催化的氧化应激作用在AD中似乎具有关键意义。AD中金属离子稳态严重失调，并且发现实验诱导的锌（II）和铜（II）稳态紊乱会影响淀粉样前体蛋白（APP）的代谢。APP本身在纳摩尔浓度下结合锌（II）和铜（II），并且认为APP代谢或表达水平的改变会导致神经毒性过程。