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Comput Struct Biotechnol J. 2014 Dec 15;13:95-100. doi: 10.1016/j.csbj.2014.12.004. eCollection 2015.

Tissue-nonspecific Alkaline Phosphatase Regulates Purinergic Transmission in the Central Nervous System During Development and Disease.

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Department of Biochemistry and Molecular Biology, Veterinary School, Complutense University of Madrid, Avda. Puerta de Hierro S/N, 28040 Madrid, Spain ; Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, IdISSC, Madrid, Spain.
Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain ; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), Madrid, Spain.
Institute of Cell Biology and Neuroscience, Molecular and Cellular Neurobiology, J. W. Goethe-University, Frankfurt 60438, Germany.
Sanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, United States.


Tissue-nonspecific alkaline phosphatase (TNAP) is one of the four isozymes in humans and mice that have the capacity to hydrolyze phosphate groups from a wide spectrum of physiological substrates. Among these, TNAP degrades substrates implicated in neurotransmission. Transgenic mice lacking TNAP activity display the characteristic skeletal and dental phenotype of infantile hypophosphatasia, as well as spontaneous epileptic seizures and die around 10 days after birth. This physiopathology, linked to the expression pattern of TNAP in the central nervous system (CNS) during embryonic stages, suggests an important role for TNAP in neuronal development and synaptic function, situating it as a good target to be explored for the treatment of neurological diseases. In this review, we will focus mainly on the role that TNAP plays as an ectonucleotidase in CNS regulating the levels of extracellular ATP and consequently purinergic signaling.


ATP; Development; Neurodegenerative diseases; P2X7R; Pyridoxal phosphate; TNAP

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