过氧化物还原家族蛋白与肾脏病的研究进展

Research Advances in Peroxiredoxin (PRDX) Family Proteins and Kidney Diseases

关键词:  过氧化物还原蛋白  肾脏病  氧化应激  治疗靶点

Key words:  peroxiredoxin  kidney diseases  oxidative stress  therapeutic targets

摘要:

本综述首次系统梳理了过氧化物还原蛋白（PRDX）家族在肾脏疾病中的多层面作用，提供了该领域研究的新视角。自1987年发现以来，PRDX因其独特的抗氧化机制和结构特征备受关注。该家族成员依赖保守半胱氨酸残基还原过氧化物，并根据结构特征分为2-Cys、非典型2-Cys和1-Cys三个亚型。PRDX在调控氧化应激中扮演核心角色，其功能与多种肾脏疾病的发生发展密切相关。研究表明，血清PRDX水平可作为评估慢性肾脏病及急性肾损伤风险的氧化应激生物标志物；同时，不同PRDX亚型在各类肾小球肾炎中表现出特异性功能。此外，组织中PRDX1-PRDX6的表达丰度与功能活性动态变化深刻影响着肾脏疾病进程。本文创新性地阐释了PRDX在肾脏病中兼具“保护盾”与“致病性”的双重作用及其精密的调控网络，并探讨了其作为诊断标志物和治疗靶点的巨大潜力及面临的转化挑战。

Abstract:

This review provides the first systematic synthesis of the multifaceted roles of the peroxiredoxin (PRDX) family in kidney diseases, offering novel perspectives for research in this field. Since their discovery in 1987, PRDXs have garnered significant attention due to their unique antioxidant mechanisms and structural characteristics. Family members rely on conserved cysteine residues to reduce peroxides and are classified into three subtypes based on structural features: 2-Cys, atypical 2-Cys, and 1-Cys. PRDXs play a central role in regulating oxidative stress, and their functions are closely linked to the onset and progression of various kidney diseases. Studies indicate that serum PRDX levels can serve as oxidative stress biomarkers for assessing the risk of chronic kidney disease (CKD) and acute kidney injury (AKI). Concurrently, different PRDX subtypes exhibit specific functions in various forms of glomerulonephritis. Furthermore, the dynamic changes in the expression abundance and functional activity of PRDX1-PRDX6 in tissues profoundly influence the course of kidney diseases.This review innovatively elucidates the dual roles of PRDXs in kidney pathologies-acting both as a “protective shield” and a pathogenic factor-along with their intricate regulatory networks. It also explores their significant potential as diagnostic biomarkers and therapeutic targets, alongside the translational challenges they present.