Guo Q, Fu W, Xie J, Luo H, Sells S F, Geddes J W, Bondada V, Rangnekar V M, Mattson M P
Sanders-Brown Research Center on Aging, University of Kentucky, Lexington 40536, USA.
Nat Med. 1998 Aug;4(8):957-62. doi: 10.1038/nm0898-957.
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. Par-4 is expressed in the nervous system, 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. 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 withdrawal. Par-4 expression was enhanced, and mitochondrial dysfunction and apoptosis exacerbated, in cells expressing presenilin-1 mutations associated with early-onset inherited AD.
前列腺凋亡反应蛋白4（Par-4）是一种同时含有亮氨酸拉链和死亡结构域的蛋白质，它是通过差异筛选在经历凋亡的前列腺癌细胞中上调的基因而分离得到的。Par-4在神经系统中表达，其功能尚不清楚。在阿尔茨海默病（AD）中，神经元可能通过凋亡死亡，淀粉样β蛋白（Aβ）可能在此过程中发挥作用。我们在此报告，Par-4在AD脑的易损神经元中表达增加，并且在经历凋亡的培养神经元中被诱导。阻断Par-4的表达或功能可预防由Aβ和营养因子撤除诱导的神经元凋亡。在表达与早发性遗传性AD相关的早老素-1突变的细胞中，Par-4表达增强，线粒体功能障碍和凋亡加剧。
