Department of Pharmacology, Saveetha Institute of Medical and Technical Sciences, Saveetha Dental College and Hospitals, Saveetha University, Chennai 600 077, Tamil Nadu, India.
Centre for Biotechnology, Anna University, Chennai 600 025, Tamil Nadu, India.
Biomolecules. 2021 Oct 21;11(11):1564. doi: 10.3390/biom11111564.
Tissue-nonspecific alkaline phosphatase (TNAP) is a key enzyme responsible for skeletal tissue mineralization. It is involved in the dephosphorylation of various physiological substrates, and has vital physiological functions, including extra-skeletal functions, such as neuronal development, detoxification of lipopolysaccharide (LPS), an anti-inflammatory role, bile pH regulation, and the maintenance of the blood brain barrier (BBB). TNAP is also implicated in ectopic pathological calcification of soft tissues, especially the vasculature. Although it is the crucial enzyme in mineralization of skeletal and dental tissues, it is a logical clinical target to attenuate vascular calcification. Various tools and studies have been developed to inhibit its activity to arrest soft tissue mineralization. However, we should not neglect its other physiological functions prior to therapies targeting TNAP. Therefore, a better understanding into the mechanisms mediated by TNAP is needed for minimizing off targeted effects and aid in the betterment of various pathological scenarios. In this review, we have discussed the mechanism of mineralization and functions of TNAP beyond its primary role of hard tissue mineralization.
组织非特异性碱性磷酸酶（TNAP）是一种负责骨骼组织矿化的关键酶。它参与各种生理底物的去磷酸化，具有重要的生理功能，包括骨骼外功能，如神经元发育、脂多糖（LPS）解毒、抗炎作用、胆汁 pH 调节和血脑屏障（BBB）的维持。TNAP 也与软组织的异位病理性钙化有关，特别是血管。尽管它是骨骼和牙齿组织矿化的关键酶，但抑制血管钙化是一个合理的临床靶点。已经开发了各种工具和研究来抑制其活性以阻止软组织矿化。然而，在针对 TNAP 的治疗之前，我们不应该忽视其其他生理功能。因此，为了最小化脱靶效应并帮助改善各种病理情况，需要更好地了解 TNAP 介导的机制。在这篇综述中，我们讨论了 TNAP 的矿化机制和除了其主要的硬组织矿化作用之外的功能。
