Neuroprotection by dehydroepiandrosterone-sulfate:: role of an NFκB-like factor
Neuroprotection by dehydroepiandrosterone-sulfate:: role of an NFκB-like factor
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DOI：
10.1097/00001756-199803090-00036
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发表时间：
1998-03-09
期刊：
影响因子：
1.7
通讯作者：
Barger, SW
中科院分区：
文献类型：
--
作者：
Mao, XR;Barger, SW
脱氢表雄酮（DHEA）及其硫酸衍生物（DHEA- s）的水平随着年龄的增长而下降，在阿尔茨海默病（AD）中达到更低的水平。先前发表的DHEA和DHEA- s对未挑战神经元存活的影响使我们在兴奋性毒性范例中对它们进行了测试。虽然DHEA- s保护海马神经元对抗谷氨酸，但同等剂量的DHEA本身几乎没有保护作用。这种神经保护差异与DHEA- s（但不是DHEA）提高kappa b依赖性转录因子活性的能力是一致的，这是我们之前与神经保护有关的现象。此外，通过“诱饵”寡核苷酸抑制kappa B dna结合可阻断DHEA-S的神经保护活性。这些发现表明，与年龄相关的DHEA-S可用性下降可能会加剧神经毒性，并且数据表明，通过药理操作神经元中kappa b依赖性转录可能获得治疗效果。
LEVELS of dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEA-S) decline during aging and reach even lower levels in Alzheimer's disease (AD). Previously published effects of DHEA and DHEA-S on unchallenged neuronal survival led us to test them in an excitotoxicity paradigm. While DHEA-S protected hippocampal neurons against glutamate, little protection was observed with equivalent doses of DHEA itself. This differential neuroprotection was consistent with the ability of DHEA-S (but not DHEA) to elevate a kappa B-dependent transcription factor activity, a phenomenon we previously have connected with neuroprotection. Furthermore, suppression of kappa B DNA-binding by 'decoy' oligonucleotides blocked the neuroprotective activity of DHEA-S. These findings imply that age-related declines in the availability of DHEA-S could exacerbate neurotoxicity, and the data suggest that therapeutic gains may be obtained with pharmacological manipulation of kappa B-dependent transcription in neurons.