缺氧诱导因子-脯氨酰羟化酶在衰老和疾病中的作用

IF 12.5 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews Pub Date : 2024-10-22 DOI:10.1016/j.arr.2024.102551

Fedor Galkin , Fadi E. Pulous , Yanyun Fu , Man Zhang , Frank W. Pun , Feng Ren , Alex Zhavoronkov

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引用次数: 0

摘要

含脯氨酰羟化酶结构域（PHD 或 EGL9-同源物）酶家族主要因其在细胞应对缺氧过程中的作用而闻名。HIF-PH 抑制剂可稳定低氧诱导因子（HIFs），激活转录程序，促进血管生成和红细胞生成等过程，以适应氧含量的变化。HIF-PH 抑制剂已被临床批准用于治疗多种类型的贫血症。虽然有关 HIF-PH 信号轴的讨论大多集中在低氧条件下，但越来越多的人认识到它在常氧条件下的重要性。PHD 生物学的最新进展突显了针对这一通路治疗一系列衰老相关疾病的潜力。在本文中，我们将回顾这些最新发现，将它们置于衰老和疾病的大背景下，并探讨针对这些适应症的 PHD 酶的当前治疗策略。

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Roles of hypoxia-inducible factor-prolyl hydroxylases in aging and disease

The prolyl hydroxylase domain-containing (PHD or EGL9-homologs) enzyme family is mainly known for its role in the cellular response to hypoxia. HIF-PH inhibitors can stabilize hypoxia-inducible factors (HIFs), activating transcriptional programs that promote processes such as angiogenesis and erythropoiesis to adapt to changes in oxygen levels. HIF-PH inhibitors have been clinically approved for treating several types of anaemia. While most discussions of the HIF-PH signalling axis focus on hypoxia, there is a growing recognition of its importance under normoxic conditions. Recent advances in PHD biology have highlighted the potential of targeting this pathway therapeutically for a range of aging-related diseases. In this article, we review these recent discoveries, situate them within the broader context of aging and disease, and explore current therapeutic strategies that target PHD enzymes for these indications.

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来源期刊

Ageing Research Reviews 医学-老年医学

CiteScore

19.80

自引率

2.30%

发文量

216

审稿时长

55 days

期刊介绍： With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.