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热休克蛋白90作为视网膜疾病的潜在治疗靶点

Hsp90 as a Potential Therapeutic Target in Retinal Disease.

作者信息

Aguilà Mònica, Cheetham Michael E

机构信息

Department of Ocular Biology and Therapeutics, UCL Institute of Ophthalmology, 11-43 Bath Street, EC1V 9EL, London, UK.

出版信息

Adv Exp Med Biol. 2016;854:161-7. doi: 10.1007/978-3-319-17121-0_22.

Abstract

The molecular chaperone heat shock protein 90 (Hsp90) is a pivotal cellular regulator involved in the folding, activation and assembly of a wide range of proteins. Hsp90 has multiple roles in the retina and the use of different Hsp90 inhibitors has been shown to prevent retinal degeneration in models of retinitis pigmentosa and age-related macular degeneration. Hsp90 is also a potential target in uveal melanoma. Mechanistically, Hsp90 inhibition can evoke a dual response in the retina; stimulating a stress response with molecular chaperone expression. Thereby leading to an improvement in visual function and photoreceptor survival; however, prolonged inhibition can also stimulate the degradation of Hsp90 client proteins potentially deleteriously affect vision. Here, we review the multiple roles of Hsp90 in the retina and the therapeutic potential of Hsp90 as a target.

摘要

分子伴侣热休克蛋白90(Hsp90)是一种关键的细胞调节因子,参与多种蛋白质的折叠、激活和组装。Hsp90在视网膜中具有多种作用,并且已证明使用不同的Hsp90抑制剂可预防色素性视网膜炎和年龄相关性黄斑变性模型中的视网膜变性。Hsp90也是葡萄膜黑色素瘤的一个潜在靶点。从机制上讲,Hsp90抑制可在视网膜中引发双重反应;通过分子伴侣表达刺激应激反应。从而导致视觉功能和光感受器存活率提高;然而,长期抑制也可刺激Hsp90客户蛋白的降解,这可能对视功能产生有害影响。在此,我们综述了Hsp90在视网膜中的多种作用以及Hsp90作为靶点的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/564d/5044979/7769386987a4/emss-70060-f001.jpg

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