Heat shock treatment reduces beta amyloid toxicity in vivo by diminishing oligomers.
Heat shock treatment reduces beta amyloid toxicity in vivo by diminishing oligomers.
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DOI：
10.1016/j.neurobiolaging.2008.07.013
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发表时间：
2010-06
影响因子：
4.2
通讯作者：
Luo, Yuan
中科院分区：
文献类型：
--
作者：
Wu, Yanjue;Cao, Zhiming;Klein, William L.;Luo, Yuan
热休克反应是由热休克蛋白介导的一种高度保守的多细胞生物体恢复细胞内稳态的生理过程。热休克因子和随后的热休克蛋白的表达在无脊椎动物和脊椎动物模型中对蛋白毒性的保护中起作用。β-淀粉样肽（Aβ）寡聚化引起的蛋白毒性与阿尔茨海默病的发病机制有关。以前，我们证明了在转基因C.通过Aβ寡聚体抑制剂银杏叶提取物及其成分减轻了线虫的感染（Wu，et al.，J. Neurosci 2006，26：13102-13）。在本研究中，我们对转基因的C. elegans并演示：1）瘫痪显著延迟，2）小热休克蛋白HSP 16.2表达增加，3）Aβ寡聚体以热休克时间依赖性方式显著减少。这些结果表明，短暂热休克通过减少Aβ寡聚化来减轻Aβ毒性，这提供了内源性伴侣蛋白上调与体内Aβ蛋白毒性保护之间的联系。
Heat shock response, mediated by heat shock proteins, is a highly conserved physiological process in multicellular organisms for reestablishment of cellular homeostasis. Expression of heat shock factors and subsequent heat shock protein plays a role in protection against proteotoxicity in invertebrate and vertebrate models. Proteotoxicity due to β-amyloid peptide (Aβ) oligomerization has been linked to the pathogenesis of Alzheimer's disease. Previously, we demonstrated that progressive paralysis induced by expression of human Aβ1-42 in transgenic C. elegans was alleviated by Aβ oligomer inhibitors ginkgo biloba extract and its constituents (Wu, et al., J. Neurosci 2006, 26:13102-13). In this study, we apply a protective heat shock to the transgenic C. elegans and demonstrate: 1) a remarkable delay in paralysis, 2) increased expression of small heat shock protein HSP16.2, and 3) significant reduction of Aβ oligomers in a heat shock time-dependent manner. These results suggest that transient heat shock lessens Aβ toxicity by diminishing Aβ oligomerization, which provide a link between up regulation of endogenous chaperone proteins and protection against Aβ proteotoxicity in vivo.
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