ENPP1 in Blood and Bone: Skeletal and Soft Tissue Diseases Induced by ENPP1 Deficiency.

IF 28.4 1区医学 Q1 PATHOLOGY Annual Review of Pathology-Mechanisms of Disease Pub Date : 2024-01-24 Epub Date: 2023-10-23 DOI:10.1146/annurev-pathmechdis-051222-121126

Carlos R Ferreira, Thomas O Carpenter, Demetrios T Braddock

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Abstract

The enzyme ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) codes for a type 2 transmembrane glycoprotein that hydrolyzes extracellular ATP to generate pyrophosphate (PP_i) and adenosine monophosphate, thereby contributing to downstream purinergic signaling pathways. The clinical phenotypes induced by ENPP1 deficiency are seemingly contradictory and include early-onset osteoporosis in middle-aged adults and life-threatening vascular calcifications in the large arteries of infants with generalized arterial calcification of infancy. The progressive overmineralization of soft tissue and concurrent undermineralization of skeleton also occur in the general medical population, where it is referred to as paradoxical mineralization to highlight the confusing pathophysiology. This review summarizes the clinical presentation and pathophysiology of paradoxical mineralization unveiled by ENPP1 deficiency and the bench-to-bedside development of a novel ENPP1 biologics designed to treat mineralization disorders in the rare disease and general medical population.

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血液和骨骼中的ENPP1：由ENPP1缺乏引起的骨骼和软组织疾病。

外核苷酸焦磷酸酶/磷酸二酯酶-1（ENPP1）编码2型跨膜糖蛋白，该糖蛋白水解细胞外ATP产生焦磷酸（PPi）和单磷酸腺苷，从而促进下游嘌呤能信号通路。ENPP1缺乏引起的临床表型似乎是矛盾的，包括中年人的早发性骨质疏松症和婴儿大动脉中危及生命的血管钙化以及婴儿期的广泛动脉钙化。软组织的渐进性过度矿化和骨骼的同时矿化不足也发生在普通医学人群中，这被称为反常矿化，以突出令人困惑的病理生理学。这篇综述总结了ENPP1缺乏引起的反常矿化的临床表现和病理生理学，以及一种新的ENPP1生物制剂的研发，该制剂旨在治疗罕见病和普通医学人群中的矿化障碍。《病理学年度评论：疾病机制》第19卷预计最终在线出版日期为2024年1月。请参阅http://www.annualreviews.org/page/journal/pubdates用于修订估算。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annual Review of Pathology-Mechanisms of Disease 医学-病理学

CiteScore

62.60

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0.00%

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期刊介绍： The Annual Review of Pathology: Mechanisms of Disease is a scholarly journal that has been published since 2006. Its primary focus is to provide a comprehensive overview of recent advancements in our knowledge of the causes and development of significant human diseases. The journal places particular emphasis on exploring the current and evolving concepts of disease pathogenesis, as well as the molecular genetic and morphological changes associated with various diseases. Additionally, the journal addresses the clinical significance of these findings. In order to increase accessibility and promote the broad dissemination of research, the current volume of the journal has transitioned from a gated subscription model to an open access format. This change has been made possible through the Annual Reviews' Subscribe to Open program, which allows all articles published in this volume to be freely accessible to readers. As part of this transition, all articles in the journal are published under a Creative Commons Attribution (CC BY) license, which encourages open sharing and use of the research.