CHOP and the endoplasmic reticulum stress response in myelinating glia.

CHOP and the endoplasmic reticulum stress response in myelinating glia.
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DOI:
10.1016/j.conb.2009.08.007
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发表时间:
2009-10
影响因子:
5.7
通讯作者:
Wrabetz L
Wrabetz L
中科院分区:
医学2区
文献类型:
--
作者:
Gow A;Wrabetz L

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未折叠蛋白反应(UPR)包括激酶信号传导和转录因子激活级联反应,在过去的20年中描绘。大多数研究得出的结论是,这种应激反应是适应性的,但尽管如此,包括适应不良的程序,涉及CHOP表达,驱动细胞自主凋亡。在此,我们强调了几项涉及中枢和外周神经系统髓鞘形成胶质细胞的UPR疾病的研究,这些研究不支持CHOP在细胞凋亡中的主要作用。在少突胶质细胞中,CHOP表达明显保护免于死亡,而在雪旺细胞中,CHOP在没有细胞死亡的情况下促进脱髓鞘。总之,这些研究表明,CHOP应被视为更广泛的细胞和环境特异性介质的适应性或适应不良的压力反应,而不是一个促凋亡转录因子。
The unfolded protein response (UPR) comprises kinase signaling and transcription factor activation cascades delineated over the past 20 years. Most studies conclude that this stress response is adaptive but, nevertheless, includes maladaptive programs involving CHOP expression which drive cell-autonomous apoptosis. Herein, we highlight several studies of UPR diseases involving myelinating glia of the central and peripheral nervous systems that do not support a primary role for CHOP in apoptosis. In oligodendrocytes, CHOP expression apparently protects against death whereas in Schwann cells, CHOP promotes demyelination in the absence of cell death. Together, these studies demonstrate that CHOP should be viewed more broadly as a cell- and context-specific mediator of adaptive or maladaptive responses to stress rather than a proapoptotic transcription factor.
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