Heat shock protein 70 participates in the neuroprotective response to intracellularly expressed β-amyloid in neurons
Heat shock protein 70 participates in the neuroprotective response to intracellularly expressed β-amyloid in neurons
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DOI：
10.1523/jneurosci.4330-03.2004
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发表时间：
2004-02-18
影响因子：
5.3
通讯作者：
Querfurth, HW
中科院分区：
文献类型：
--
作者：
Magrané, J;Smith, RC;Querfurth, HW
细胞内β-淀粉样蛋白42（A β 42）的积累越来越多地被认为是阿尔茨海默病（AD）发病机制的早期事件。我们已经开发了一种基于多西环素诱导的腺病毒系统，该系统以受调控的方式指导细胞内Abeta 42表达和积累到原代神经元培养物的内质网中。Abeta 42在细胞体中表现出核周分布，并与囊泡隔室相关。病毒表达的细胞内Abeta 42在诱导后24小时以剂量依赖性方式对神经元培养物具有毒性。Abeta 42的表达促进了应激诱导的Hsp 70蛋白在神经元中的快速诱导，并且病毒介导的Hsp 70过表达将神经元从细胞内Abeta 42积累的毒性作用中拯救出来。总之，这些结果暗示细胞应激反应是神经元培养物中Abeta诱导毒性的可能调节剂。
Intracellular beta-amyloid 42 (Abeta42) accumulation is increasingly recognized as an early event in the pathogenesis of Alzheimer's disease (AD). We have developed a doxycycline-inducible adenoviral-based system that directs intracellular Abeta42 expression and accumulation into the endoplasmic reticulum of primary neuronal cultures in a regulated manner. Abeta42 exhibited a perinuclear distribution in cell bodies and an association with vesicular compartments. Virally expressed intracellular Abeta42 was toxic to neuronal cultures 24 hr after induction in a dose-dependent manner. Abeta42 expression prompted the rapid induction of stress-inducible Hsp70 protein in neurons, and virally mediated Hsp70 overexpression rescued neurons from the toxic effects of intracellular Abeta accumulation. Together, these results implicate the cellular stress response as a possible modulator of Abeta-induced toxicity in neuronal cultures.