APP induces neuronal apoptosis through APP-BP1-mediated downregulation of β-catenin
APP induces neuronal apoptosis through APP-BP1-mediated downregulation of β-catenin
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DOI：
10.1023/b:appt.0000031447.05354.9f
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发表时间：
2004-07-01
期刊：
影响因子：
7.2
通讯作者：
Chen, YZ
中科院分区：
文献类型：
--
作者：
Chen, YZ
阿尔茨海默病（AD）是一种与进行性痴呆相关的神经退行性疾病。这篇小综述重点关注淀粉样前体蛋白 (APP) 作为 APP-BP1/hUba3 激活的 neddylation 通路的调节因子如何在 AD 和唐氏综合症中发挥核心作用。有人认为APP的生理功能是下调β-连环蛋白的水平。然而，在 APP 和早老素有家族性 AD (FAD) 突变的患者中，这种 APP 功能异常增强，导致 neddylation 过度激活以及 β-catenin 降低至阈值水平以下。文献中的证据总结表明，APP 在下调 β-catenin 方面的功能障碍可能是 AD 和唐氏综合症中神经元死亡的机制的基础。
Alzheimer's disease (AD) is a neurodegenerative disease associated with progressive dementia. This mini-review focuses on how the amyloid precursor protein (APP) plays a central role in AD and Down syndrome as the regulator of the APP-BP1/hUba3 activated neddylation pathway. It is argued that the physiological function of APP is to downregulate the level of beta-catenin. However, this APP function is abnormally amplified in patients with familial AD ( FAD) mutations in APP and presenilins, resulting in the hyperactivation of neddylation and the decrease of beta-catenin below a threshold level. Evidence in the literature is summarized to show that dysfunction of APP in downregulating beta-catenin may underlie the mechanism of neuronal death in AD and Down syndrome.