The unfolded protein response modulates disease severity in Pelizaeus-Merzbacher disease
The unfolded protein response modulates disease severity in Pelizaeus-Merzbacher disease
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DOI：
10.1016/s0896-6273(02)01045-0
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发表时间：
2002-11-14
期刊：
影响因子：
16.2
通讯作者：
Gow, A
中科院分区：
文献类型：
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作者：
Southwood, CM;Garbern, J;Gow, A
未折叠蛋白反应（UPR）是一种真核生物信号通路，将蛋白质通量通过内质网与转录和翻译抑制联系起来。在此，我们证明了UPR在白质营养不良的Pelizaeus-Merzbacher病（PMD）以及该疾病的三种小鼠模型和表达突变蛋白的转染成纤维细胞中激活。CHOP蛋白，被广泛认为是一种促凋亡转录因子，在小鼠PMD模型中调节发病机制；然而，该蛋白表现出抗凋亡活性。总之，这些数据表明，在许多表达突变分泌通路蛋白的细胞中，UPR具有调节疾病严重程度的潜力。因此，PMD代表了一类新的不同的退行性疾病的第一个成员，UPR激活和信号传导是常见的致病机制。
The unfolded protein response (UPR) is a eukaryotic signaling pathway linking protein flux through the endoplasmic reticulum to transcription and translational repression. Herein, we demonstrate UPR activation in the leukodystrophy Pelizaeus-Merzbacher disease (PMD) as well as in three mouse models of this disease and transfected fibroblasts expressing mutant protein. The CHOP protein, widely known as a proapoptotic transcription factor, modulates pathogenesis in the mouse models of PMD; however, this protein exhibits antiapoptotic activity. Together, these data show that the UPR has the potential to modulate disease severity in many cells expressing mutant secretory pathway proteins. Thus, PMD represents the first member of a novel class of disparate degenerative diseases for which UPR activation and signaling is the common pathogenic mechanism.