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以核仁为靶点的人类疾病治疗策略。

Targeting the nucleolus as a therapeutic strategy in human disease.

机构信息

Science for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.

Genomic Instability Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.

出版信息

Trends Biochem Sci. 2023 Mar;48(3):274-287. doi: 10.1016/j.tibs.2022.09.006. Epub 2022 Oct 10.

Abstract

The nucleolus is the site of ribosome biogenesis, one of the most resource-intensive processes in eukaryotic cells. Accordingly, nucleolar morphology and activity are highly responsive to growth signaling and nucleolar insults which are collectively included in the actively evolving concept of nucleolar stress. Importantly, nucleolar alterations are a prominent feature of multiple human pathologies, including cancer and neurodegeneration, as well as being associated with aging. The past decades have seen numerous attempts to isolate compounds targeting different facets of nucleolar activity. We provide an overview of therapeutic opportunities for targeting nucleoli in different pathologies and currently available therapies.

摘要

核仁是核糖体生物发生的场所,这是真核细胞中资源最密集的过程之一。因此,核仁形态和活性对生长信号和核仁损伤高度敏感,这些损伤共同包含在不断发展的核仁应激概念中。重要的是,核仁改变是多种人类疾病的一个突出特征,包括癌症和神经退行性疾病,并且与衰老有关。在过去的几十年中,人们已经尝试了许多方法来分离针对核仁活性不同方面的化合物。我们提供了针对不同病理的核仁靶向治疗机会和当前可用疗法的概述。

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