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CCR5阻断的治疗前景不断拓展。

The Expanding Therapeutic Perspective of CCR5 Blockade.

作者信息

Vangelista Luca, Vento Sandro

机构信息

Department of Biomedical Sciences, Nazarbayev University School of Medicine, Astana, Kazakhstan.

Department of Medicine, Nazarbayev University School of Medicine and University Medical Center, Astana, Kazakhstan.

出版信息

Front Immunol. 2018 Jan 12;8:1981. doi: 10.3389/fimmu.2017.01981. eCollection 2017.

Abstract

CCR5 and its interaction with chemokine ligands have been crucial for understanding and tackling HIV-1 entry into target cells. However, over time, CCR5 has witnessed an impressive transition from being considered rather unimportant in physiology and pathology to becoming central in a growing number of pathophysiological conditions. It now turns out that the massive efforts devoted to combat HIV-1 entry by interfering with CCR5, and the subsequent production of chemokine ligand variants, small chemical compounds, and other molecular entities and strategies, may set the therapeutic standards for a wealth of different pathologies. Expressed on various cell types, CCR5 plays a vital role in the inflammatory response by directing cells to sites of inflammation. Aside HIV-1, CCR5 has been implicated in other infectious diseases and non-infectious diseases such as cancer, atherosclerosis, and inflammatory bowel disease. Individuals carrying the CCR5Δ32 mutation live a normal life and are warranted a natural barrier to HIV-1 infection. Therefore, CCR5 antagonism and gene-edited knockout of the receptor gained growing interest for the therapeutic role that CCR5 blockade may play in the attenuation of the severity or progression of numerous diseases.

摘要

CCR5及其与趋化因子配体的相互作用对于理解和应对HIV-1进入靶细胞至关重要。然而,随着时间的推移,CCR5经历了令人瞩目的转变,从在生理学和病理学中被认为相当不重要,到在越来越多的病理生理状况中变得至关重要。现在发现,通过干扰CCR5来对抗HIV-1进入以及随后产生趋化因子配体变体、小分子化合物和其他分子实体及策略所付出的巨大努力,可能为众多不同病理状况设定治疗标准。CCR5在多种细胞类型上表达,通过引导细胞至炎症部位在炎症反应中发挥重要作用。除了HIV-1,CCR5还与其他传染病和非传染病有关,如癌症、动脉粥样硬化和炎症性肠病。携带CCR5Δ32突变的个体过着正常生活,对HIV-1感染有天然屏障。因此,CCR5拮抗作用以及对该受体进行基因编辑敲除,因其在减轻多种疾病的严重程度或进展方面可能发挥的治疗作用而越来越受到关注。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e49/5770570/c251b3fbc78b/fimmu-08-01981-g001.jpg

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