Layer-specific activity of tissue non-specific alkaline phosphatase in the human neocortex

Négyessy, László; Xiao, Jian‐Kang; Kántor, Orsolya; Kovács, Gárbor G.; Palkovits, Miklós; Dóczi, Tamás; Renaud, Luc; Baksa, Gábor; Glasz, Tibor; Ashaber, Mária; Barone, Pascal; Fonta, Caroline

doi:10.1016/j.neuroscience.2010.10.049

Cited by 51 publications

(41 citation statements)

References 43 publications

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“…This activity was intense and completely abrogated with the AP inhibitor levamisole. Previous reports have demonstrated that AP activity in human brain is attributable to TNAP expression [39,40].…”

Section: Discussionmentioning

confidence: 96%

Reduced striatal ecto-nucleotidase activity in schizophrenia patients supports the “adenosine hypothesis”

Aliagas

Villar-Menéndez

Sévigny

et al. 2013

Purinergic Signalling

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Schizophrenia (SZ) is a major chronic neuropsychiatric disorder characterized by a hyperdopaminergic state. The hypoadenosinergic hypothesis proposes that reduced extracellular adenosine levels contribute to dopamine D 2 receptor hyperactivity. ATP, through the action of ecto-nucleotidases, constitutes a main source of extracellular adenosine. In the present study, we examined the activity of ecto-nucleotidases (NTPDases, ecto-5′-nucleotidase, and alkaline phosphatase) in the postmortem putamen of SZ patients (n=13) compared with aged-matched controls (n=10). We firstly demonstrated, by means of artificial postmortem delay experiments, that ectonucleotidase activity in human brains was stable up to 24 h, indicating the reliability of this tissue for these enzyme determinations. Remarkably, NTPDase-attributable activity (both ATPase and ADPase) was found to be reduced in SZ patients, while ecto-5′-nucleotidase and alkaline phosphatase activity remained unchanged. In the present study, we also describe the localization of these ecto-enzymes in human putamen control samples, showing differential expression in blood vessels, neurons, and glial cells. In conclusion, reduced striatal NTPDase activity may contribute to the pathophysiology of SZ, and it represents a potential mechanism of adenosine signalling impairment in this illness.

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Section: Discussionmentioning

confidence: 96%

Reduced striatal ecto-nucleotidase activity in schizophrenia patients supports the “adenosine hypothesis”

Aliagas

Villar-Menéndez

Sévigny

et al. 2013

Purinergic Signalling

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“…They are also expressed a Human NPP1 residue numbering is used. Numbers in brackets refer to the NPP enzyme used in the study by embryonic stem cells [465], primordial stem cells [466], in neural stem cells [55,467], in the vascular endothelium and the neuropile of the brain [319,468,469], or in hair follicles [470]. Multiple technical approaches for the heterologous expression of APs have been elaborated [471].…”

Section: Alkaline Phosphatasesmentioning

confidence: 99%

Cellular function and molecular structure of ecto-nucleotidases

Zimmermann

Zebisch

Sträter

2012

Purinergic Signalling

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922

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Ecto-nucleotidases play a pivotal role in purinergic signal transmission. They hydrolyze extracellular nucleotides and thus can control their availability at purinergic P2 receptors. They generate extracellular nucleosides for cellular reuptake and salvage via nucleoside transporters of the plasma membrane. The extracellular adenosine formed acts as an agonist of purinergic P1 receptors. They also can produce and hydrolyze extracellular inorganic pyrophosphate that is of major relevance in the control of bone mineralization. This review discusses and compares four major groups of ectonucleotidases: the ecto-nucleoside triphosphate diphosphohydrolases, ecto-5′-nucleotidase, ecto-nucleotide pyrophosphatase/phosphodiesterases, and alkaline phosphatases. Only recently and based on crystal structures, detailed information regarding the spatial structures and catalytic mechanisms has become available for members of these four ecto-nucleotidase families. This permits detailed predictions of their catalytic mechanisms and a comparison between the individual enzyme groups. The review focuses on the principal biochemical, cell biological, catalytic, and structural properties of the enzymes and provides brief reference to tissue distribution, and physiological and pathophysiological functions.

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“…It is primarily known for its role in bone growth by providing inorganic phosphate for hydroxyapatite crystal production (Robison 1923) and by hydrolyzing inorganic pyrophosphate (Whyte 2010;Moss et al 1967) which is an inhibitor of bone mineralization (Fleisch et al 1966). TNSALP is also involved in regulation of neurotransmission in the cerebral cortex (Négyessy et al 2011;Spentchian et al 2003;Whyte 2010). More than 200 mutations in the TNSALP gene have been described, 80% of these being missense mutations (Mornet 2008).…”

Section: Introductionmentioning

confidence: 99%

Infantile Hypophosphatasia Secondary to a Novel Compound Heterozygous Mutation Presenting with Pyridoxine-Responsive Seizures

et al. 2013

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Hypophosphatasia (HPP) is a rare metabolic disease with the hallmark finding of deficient serum tissue nonspecific alkaline phosphatase (TNSALP) activity. TNSALP is primarily known for its role in mineralization; hence, HPP is characterized by defective mineralization of bone and/or teeth. TNSALP is also necessary for proper vitamin B6 metabolism and its participation as a cofactor for neurotransmitters in the central nervous system. Defective TNSALP activity in the brain can result in intractable seizures responsive to pyridoxine. The pathophysiology of pyridoxine-responsive seizures (PRS) in severe HPP remains to be clearly defined. We review the case of a 2-month-old Caucasian boy presenting with seizures refractory to conventional antiepileptic medications. Empiric treatment with favorable response to pyridoxine in conjunction with severe metabolic bone disease, extremely low serum alkaline phosphatase, elevated phosphoethanolamine, hypercalcemia, hypercalciuria, and nephrocalcinosis led to a clinical diagnosis of infantile HPP. Sequence analysis revealed compound heterozygosity of the TNSALP gene with a novel mutation in exon 9 and a previously reported mutation in exon 12. This case reminds the physician that severe infantile HPP can present with PRS as its major initial manifestation and should alert clinicians to consider HPP in their differential of PRS. In addition, despite this severe genotype, the clinical diagnosis of our patient was delayed because of minimal phenotypic features initially. This highlights that the phenotypegenotype correlation could be variable even in severe disease. This case also demonstrates that HPP should be classified as PRS and not a form of pyridoxine-dependent epilepsy (PDE) as our patient was able to stop the pyridoxine supplementation without seizure recurrence once enzyme replacement was initiated. With the advent of enzyme replacement therapy, this once fatal disease may have improved morbidity and mortality.

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Layer-specific activity of tissue non-specific alkaline phosphatase in the human neocortex

Cited by 51 publications

References 43 publications

Reduced striatal ecto-nucleotidase activity in schizophrenia patients supports the “adenosine hypothesis”

Reduced striatal ecto-nucleotidase activity in schizophrenia patients supports the “adenosine hypothesis”

Cellular function and molecular structure of ecto-nucleotidases

Infantile Hypophosphatasia Secondary to a Novel Compound Heterozygous Mutation Presenting with Pyridoxine-Responsive Seizures

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