Par-4 is a mediator of neuronal degeneration associated with the pathogenesis of Alzheimer disease
Par-4 is a mediator of neuronal degeneration associated with the pathogenesis of Alzheimer disease
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DOI：
10.1038/nm0898-957
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发表时间：
1998-08-01
期刊：
影响因子：
82.9
通讯作者：
Mattson, MP
中科院分区：
文献类型：
--
作者：
Guo, Q;Fu, WM;Mattson, MP
前列腺细胞凋亡反应-4（Par-4）是一种含有亮氨酸拉链和死亡结构域的蛋白质，通过对经历细胞凋亡的前列腺癌细胞中上调的基因进行差异筛选而分离（1，2）。Par-4在神经系统中表达（3），其功能尚不清楚。在阿尔茨海默病（AD）中，神经元可能因细胞凋亡而死亡，淀粉样β蛋白（A β）可能在其中发挥作用（4-11）。我们在这里报告说，Par-4表达增加，在AD脑脆弱的神经元，并诱导培养的神经元进行凋亡。阻断Par-4的表达或功能可防止由Ab和营养因子撤除诱导的神经元凋亡。Par-4表达增强，线粒体功能障碍和细胞凋亡加剧，在细胞表达早老素-1突变与早发性遗传性AD。
Prostate apoptosis response-4 (Par-4) is a protein containing both a leucine zipper and a death domain that was isolated by differential screening for genes upregulated in prostate cancer cells undergoing apoptosis(1,2). Par-4 is expressed in the nervous system(3), where its function is unknown. In Alzheimer disease (AD), neurons may die by apoptosis, and amyloid beta-protein (A beta) may play a role in this(4-11). We report here that Par-4 expression is increased in vulnerable neurons in AD brain and is induced in cultured neurons undergoing apoptosis. Blockade of Par-4 expression or function prevented neuronal apoptosis induced by Ab and trophic factor withdrawl. Par-4 expression was enhanced, and mitochondrial dysfunction and apoptosis exacerbated, in cells expressing presenilin-1 mutations associated with early-onset inherited AD.