乳铁蛋白:从结构到铁稳态的功能协调。

Lactoferrin: from the structure to the functional orchestration of iron homeostasis.

机构信息

Department of Biosciences and Territory, University of Molise, Pesche, Italy.

Department of Public Health and Infectious Diseases, University of Rome La Sapienza, Rome, Italy.

出版信息

Biometals. 2023 Jun;36(3):391-416. doi: 10.1007/s10534-022-00453-x. Epub 2022 Oct 10.

Abstract

Iron is by far the most widespread and essential transition metal, possessing crucial biological functions for living systems. Despite chemical advantages, iron biology has forced organisms to face with some issues: ferric iron insolubility and ferrous-driven formation of toxic radicals. For these reasons, acquisition and transport of iron constitutes a formidable challenge for cells and organisms, which need to maintain adequate iron concentrations within a narrow range, allowing biological processes without triggering toxic effects. Higher organisms have evolved extracellular carrier proteins to acquire, transport and manage iron. In recent years, a renewed interest in iron biology has highlighted the role of iron-proteins dysregulation in the onset and/or exacerbation of different pathological conditions. However, to date, no resolutive therapy for iron disorders has been found. In this review, we outline the efficacy of Lactoferrin, a member of the transferrin family mainly secreted by exocrine glands and neutrophils, as a new emerging orchestrator of iron metabolism and homeostasis, able to counteract iron disorders associated to different pathologies, including iron deficiency and anemia of inflammation in blood, Parkinson and Alzheimer diseases in the brain and cystic fibrosis in the lung.

摘要

铁是迄今为止最广泛和最基本的过渡金属,对生命系统具有至关重要的生物学功能。尽管具有化学优势,但铁生物学迫使生物面临一些问题:三价铁不溶性和二价铁驱动的有毒自由基形成。出于这些原因,铁的获取和运输对细胞和生物构成了巨大的挑战,它们需要在狭窄的范围内维持足够的铁浓度,以允许生物过程而不会引发毒性作用。高等生物已经进化出细胞外载体蛋白来获取、运输和管理铁。近年来,人们对铁生物学的兴趣重新燃起,强调了铁蛋白失调在不同病理状况的发生和/或恶化中的作用。然而,迄今为止,还没有找到针对铁紊乱的有效治疗方法。在这篇综述中,我们概述了乳铁蛋白作为转铁蛋白家族的一员的功效,乳铁蛋白主要由外分泌腺和中性粒细胞分泌,是铁代谢和平衡的新出现的协调因子,能够对抗与不同病理相关的铁紊乱,包括血液中的缺铁和炎症性贫血、大脑中的帕金森病和阿尔茨海默病以及肺部的囊性纤维化。

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