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The metastasis-promoting S100A4 protein confers neuroprotection in brain injury

zhangxia111 添加于 2012/11/20 13:56:48  745次阅读 | 0次推荐 | 0个评论

Identification of novel pro-survival factors in the brain is paramount for developing neuroprotective therapies. The multifunctional S100 family proteins have important roles in many human diseases and are also upregulated by brain injury. However, S100 functions in the nervous system remain unclear. Here we show that the S100A4 protein, mostly studied in cancer, is overexpressed in the damaged human and rodent brain and released from stressed astrocytes. Genetic deletion of S100A4 exacerbates neuronal loss after brain trauma or excitotoxicity, increasing oxidative cell damage and downregulating the neuroprotective protein metallothionein I+II. We identify two neurotrophic motifs in S100A4 and show that these motifs are neuroprotective in animal models of brain trauma. Finally, we find that S100A4 rescues neurons via the Janus kinase/STAT pathway and, partially, the interleukin-10 receptor. Our data introduce S100A4 as a therapeutic target in neurodegeneration, and raise the entire S100 family as a potentially important factor in central nervous system injury.

作 者:Oksana Dmytriyeva, Stanislava Pankratova, Sylwia Owczarek, Katrin Sonn, Vladislav Soroka, Christina M. Ridley, Alexander Marsolais, Marcos Lopez-Hoyos, Noona Ambartsumian, Eugene Lukanidin, Elisabeth Bock, Vladimir Berezin & Darya Kiryushko
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学科领域:生命科学 » 生物物理、生物化学与分子生物学 » 蛋白质组学
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原文链接:http://www.nature.com/ncomms/journal/v3/n11/full/ncomms2202.html
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