Targeted heat shock protein 72 for pulmonary cytoprotection.

Targeted heat shock protein 72 for pulmonary cytoprotection.
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DOI:
10.1111/nyas.13059
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发表时间:
2016-06
影响因子:
5.2
通讯作者:
Richieri RA
Richieri RA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Parseghian MH;Hobson ST;Richieri RA

文献摘要

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热休克蛋白72(HSP72)可能是HSP70家族中最重要的成员,因为它在广泛的组织和细胞中被诱导来对抗应激,特别是氧化应激。在这里,我们回顾了对这种蛋白作为肺细胞保护剂的关键作用的独立观察,并讨论了开发HSP72作为创伤事件后快速输送到细胞和组织的治疗方法的优点。我们还讨论了HSP72与来源于mAb3E10的细胞穿透性单链抗体(ScFv)片段的融合,称为Fv-HSP70。这种融合结构已经在活体脑梗塞模型中得到验证,目前正在测试中,作为治疗缺血性事件的临床治疗方法,以及作为治疗由恐怖行动或工业事故导致的毒物吸入的可现场医学对策。
Heat shock protein 72 (HSP72) is perhaps the most important member of the HSP70 family of proteins, given that it is induced in a wide variety of tissues and cells to combat stress, particularly oxidative stress. Here we review independent observations of the critical role this protein plays as a pulmonary cytoprotectant and discuss the merits of developing HSP72 as a therapeutic for rapid delivery to cells and tissues after a traumatic event. We also discuss the fusion of HSP72 to a cell-penetrating single-chain Fv (scFv) antibody fragment derived from mAb 3E10, referred to as Fv-HSP70. This fusion construct has been validated in vivo in a cerebral infarction model and is currently in testing as a clinical therapeutic to treat ischemic events and as a fieldable medical countermeasure to treat inhalation of toxicants caused by terrorist actions or industrial accidents.