Alkaline Phosphatase, an Unconventional Immune Protein.
Alkaline Phosphatase, an Unconventional Immune Protein.
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DOI：
10.3389/fimmu.2017.00897
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发表时间：
2017
影响因子：
7.3
通讯作者：
Rader BA
中科院分区：
文献类型：
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作者：
Rader BA
近年来，针对碱性磷酸酶（AP）的研究越来越多，揭示了这些酶功能的复杂性。在四种人类AP（hAP）蛋白中，已知的最多的是组织非特异性AP（TNAP）和肠AP（IAP）。本审查强调了目前对TNAP和IAP与人类健康和疾病关系的理解。TNAP在多个过程中发挥作用，包括骨矿化、维生素B6代谢和神经发生，是低磷酸酶症的遗传原因，通过调节嘌呤能信号传导影响炎症，并与阿尔茨海默病有关。IAP调节脂肪酸的吸收，并与饮食诱导的肥胖和代谢综合征的调节有关。IAP和TNAP可以使细菌来源的脂多糖去磷酸化，IAP已被确定为肠道微生物组组成的潜在调节剂，这是一种进化上保守的功能。目前正在探索内源性和重组牛AP和重组hAP作为治疗AP相关疾病和减轻多种炎症来源的药理学试剂的潜力。对这些多功能蛋白质的继续研究无疑将为人类病理生理学，生物化学和人类全生物提供深入了解。
Recent years have seen an increase in the number of studies focusing on alkaline phosphatases (APs), revealing an expanding complexity of function of these enzymes. Of the four human AP (hAP) proteins, most is known about tissue non-specific AP (TNAP) and intestinal AP (IAP). This review highlights current understanding of TNAP and IAP in relation to human health and disease. TNAP plays a role in multiple processes, including bone mineralization, vitamin B6 metabolism, and neurogenesis, is the genetic cause of hypophosphatasia, influences inflammation through regulation of purinergic signaling, and has been implicated in Alzheimer’s disease. IAP regulates fatty acid absorption and has been implicated in the regulation of diet-induced obesity and metabolic syndrome. IAP and TNAP can dephosphorylate bacterial-derived lipopolysaccharide, and IAP has been identified as a potential regulator of the composition of the intestinal microbiome, an evolutionarily conserved function. Endogenous and recombinant bovine APs and recombinant hAPs are currently being explored for their potential as pharmacological agents to treat AP-associated diseases and mitigate multiple sources of inflammation. Continued research on these versatile proteins will undoubtedly provide insight into human pathophysiology, biochemistry, and the human holobiont.