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表观基因组修饰物和代谢重排:治疗学的新前沿。

Epigenome modifiers and metabolic rewiring: New frontiers in therapeutics.

机构信息

Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milano, Italy.

Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milano, Italy.

出版信息

Pharmacol Ther. 2019 Jan;193:178-193. doi: 10.1016/j.pharmthera.2018.08.008. Epub 2018 Aug 17.

Abstract

In the last decade numerous publications highlighted the connection between metabolism and epigenetics in different physiological and pathological conditions. The availability of metabolites for cells represents indeed a crucial factor, which is able to condition cell fate and development, differentiation and proliferation partially trough epigenetic control. This tight link provides novel therapeutic possibilities to treat many pathological conditions induced by epigenetic alterations, by manipulating metabolic pathways producing metabolites that work also as epigenetic modifiers. This review will explore specifically the relevance of epigenetics and metabolism in the onset of metabolic disorders and cancer, highlighting potential epigenetic-based pharmacological approaches for the treatment of these disorders trough a rewiring of cellular metabolism. We will also report recent studies on stem cells, demonstrating how epigenetic setting is influenced by metabolism and how these processes affect cell pluripotency and differentiation capacity. These findings suggest a big pharmacological potential, as the modulation of epigenetics and metabolism in stem cells may represent a new tool for regenerative medicine, offering a plethora of novel possibilities for the treatment of severe pathological conditions.

摘要

在过去的十年中,大量出版物强调了代谢与不同生理和病理条件下的表观遗传学之间的联系。事实上,细胞可用的代谢物是一个关键因素,它能够通过表观遗传控制部分调节细胞命运和发育、分化和增殖。这种紧密联系为治疗许多由表观遗传改变引起的病理状况提供了新的治疗可能性,通过操纵产生代谢物的代谢途径,这些代谢物也可以作为表观遗传修饰剂。这篇综述将特别探讨代谢和表观遗传学在代谢紊乱和癌症发病中的相关性,强调通过细胞代谢的重排来治疗这些疾病的潜在基于表观遗传的药理学方法。我们还将报告最近关于干细胞的研究,表明代谢如何影响表观遗传设置,以及这些过程如何影响细胞多能性和分化能力。这些发现表明了巨大的药理学潜力,因为在干细胞中调节表观遗传学和代谢可能代表再生医学的新工具,为严重病理状况的治疗提供了大量新的可能性。

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