淀粉样前体蛋白（APP）转基因小鼠的突触传递和学习缺陷需要APP的C末端切割。
Deficits in synaptic transmission and learning in amyloid precursor protein (APP) transgenic mice require C-terminal cleavage of APP.
作者信息
Saganich Michael J, Schroeder Brock E, Galvan Veronica, Bredesen Dale E, Koo Edward H, Heinemann Stephen F
机构信息
Salk Institute for Biological Studies, La Jolla, California 92037, USA.
出版信息
J Neurosci. 2006 Dec 27;26(52):13428-36. doi: 10.1523/JNEUROSCI.4180-06.2006.
Abstract
Synaptic dysfunction has been shown to be one of the earliest correlates of disease progression in animal models of Alzheimer's disease. Amyloid-beta protein (Abeta) is thought to play an important role in disease-related synaptic dysfunction, but the mechanism by which Abeta leads to synaptic dysfunction is not understood. Here we describe evidence that cleavage of APP in the C terminus may be necessary for the deficits present in APP transgenic mice. In APP transgenic mice with a mutated cleavage site at amino acid 664, normal synaptic transmission, synaptic plasticity, and learning were maintained despite the presence of elevated levels of APP, Abeta42, and even plaque accumulation. These results indicate that cleavage of APP may play a critical role in the development of synaptic and behavioral dysfunction in APP transgenic mice.
摘要
在阿尔茨海默病动物模型中，突触功能障碍已被证明是疾病进展的最早相关因素之一。β淀粉样蛋白（Aβ）被认为在与疾病相关的突触功能障碍中起重要作用，但Aβ导致突触功能障碍的机制尚不清楚。在此，我们描述了证据表明APP在C末端的切割可能是APP转基因小鼠中存在的缺陷所必需的。在氨基酸664处具有突变切割位点的APP转基因小鼠中，尽管APP、Aβ42水平升高甚至有斑块积累，但仍维持了正常的突触传递、突触可塑性和学习能力。这些结果表明，APP的切割可能在APP转基因小鼠的突触和行为功能障碍的发展中起关键作用。
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