The novel HSP90 inhibitor, PU-H71, suppresses glial cell activation but weakly affects clinical signs of EAE.

The novel HSP90 inhibitor, PU-H71, suppresses glial cell activation but weakly affects clinical signs of EAE.
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DOI:
10.1016/j.jneuroim.2012.10.008
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发表时间:
2013-02-15
影响因子:
3.3
通讯作者:
Dello Russo, Cinzia
Dello Russo, Cinzia
中科院分区:
医学4区
文献类型:
--
作者:
Lisi, Lucia;McGuire, Susan;Sharp, Anthony;Chiosis, Gabriela;Navarra, Pierluigi;Feinstein, Douglas L.;Dello Russo, Cinzia

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安莎霉素是非常有效的HSP 90抑制剂,在治疗EAE中显示出显著的有益效果。然而,它们的毒性和在溶液中的差稳定性限制了它们的临床应用。在本研究中,我们已经确定了一种新的HSP 90抑制剂PU-H71的抗炎特性,并测试了其在EAE中的作用。我们的研究结果表明,PU-H71减少脂多糖星形胶质细胞的活化,但未能减少炎症细胞因子的活化。与安莎霉素相比,PU-H71对EAE临床进程的影响较弱。总之,尽管PU-H71显示出一些抗炎特性,但它在体内的效果似乎不如毒性更大的HSP 90抑制剂。
Ansamycins are very effective HSP90 inhibitors that showed significant beneficial effects in the treatment of EAE. However, their toxicity and poor stability in solution limit their clinical use. In the present study we have characterized the anti-inflammatory properties of a novel HSP90 inhibitor, PU-H71, and tested its effects in EAE. Our findings show that PU-H71 reduced lipopolysaccharide astrocyte activation but failed to reduce the inflammatory cytokine activation. In contrast to ansamycins, PU-H71 weakly affects EAE clinical course. In conclusion, although PU-H71 displayed some anti-inflammatory properties, it appeared in vivo less effective than the more toxic HSP90 inhibitors.
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