@article{LiedtkeHofmannJakobetal.2020,
  author    = {Liedtke, Daniel and Hofmann, Christine and Jakob, Franz and Klopocki, Eva and Graser, Stephanie},
  title     = {Tissue-Nonspecific Alkaline Phosphatase—A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease},
  series = {Biomolecules},
  volume    = {10},
  journal   = {Biomolecules},
  number    = {12},
  publisher = {MDPI},
  issn      = {2218-273X},
  doi       = {10.3390/biom10121648},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-220096},
  year      = {2020},
  abstract  = {Tissue-nonspecific alkaline phosphatase (TNAP) is a ubiquitously expressed enzyme that is best known for its role during mineralization processes in bones and skeleton. The enzyme metabolizes phosphate compounds like inorganic pyrophosphate and pyridoxal-5′-phosphate to provide, among others, inorganic phosphate for the mineralization and transportable vitamin B6 molecules. Patients with inherited loss of function mutations in the ALPL gene and consequently altered TNAP activity are suffering from the rare metabolic disease hypophosphatasia (HPP). This systemic disease is mainly characterized by impaired bone and dental mineralization but may also be accompanied by neurological symptoms, like anxiety disorders, seizures, and depression. HPP characteristically affects all ages and shows a wide range of clinical symptoms and disease severity, which results in the classification into different clinical subtypes. This review describes the molecular function of TNAP during the mineralization of bones and teeth, further discusses the current knowledge on the enzyme's role in the nervous system and in sensory perception. An additional focus is set on the molecular role of TNAP in health and on functional observations reported in common laboratory vertebrate disease models, like rodents and zebrafish.},
  language  = {en}
}
@article{OhlebuschBorstFrankenbachetal.2020,
  author    = {Ohlebusch, Barbara and Borst, Angela and Frankenbach, Tina and Klopocki, Eva and Jakob, Franz and Liedtke, Daniel and Graser, Stephanie},
  title     = {Investigation of alpl expression and Tnap-activity in zebrafish implies conserved functions during skeletal and neuronal development},
  series = {Scientific Reports},
  volume    = {10},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-020-70152-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230024},
  year      = {2020},
  abstract  = {Hypophosphatasia (HPP) is a rare genetic disease with diverse symptoms and a heterogeneous severity of onset with underlying mutations in the ALPL gene encoding the ectoenzyme Tissue-nonspecific alkaline phosphatase (TNAP). Considering the establishment of zebrafish (Danio rerio) as a new model organism for HPP, the aim of the study was the spatial and temporal analysis of alpl expression in embryos and adult brains. Additionally, we determined functional consequences of Tnap inhibition on neural and skeletal development in zebrafish. We show that expression of alpl is present during embryonic stages and in adult neuronal tissues. Analyses of enzyme function reveal zones of pronounced Tnap-activity within the telencephalon and the mesencephalon. Treatment of zebrafish embryos with chemical Tnap inhibitors followed by axonal and cartilage/mineralized tissue staining imply functional consequences of Tnap deficiency on neuronal and skeletal development. Based on the results from neuronal and skeletal tissue analyses, which demonstrate an evolutionary conserved role of this enzyme, we consider zebrafish as a promising species for modeling HPP in order to discover new potential therapy strategies in the long-term.},
  language  = {en}
}
@article{GraserLiedtkeJakob2021,
  author    = {Graser, Stephanie and Liedtke, Daniel and Jakob, Franz},
  title     = {TNAP as a new player in chronic inflammatory conditions and metabolism},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {2},
  issn      = {1422-0067},
  doi       = {10.3390/ijms22020919},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258888},
  year      = {2021},
  abstract  = {This review summarizes important information on the ectoenzyme tissue-nonspecific alkaline phosphatase (TNAP) and gives a brief insight into the symptoms, diagnostics, and treatment of the rare disease Hypophosphatasia (HPP), which is resulting from mutations in the TNAP encoding ALPL gene. We emphasize the role of TNAP beyond its well-known contribution to mineralization processes. Therefore, above all, the impact of the enzyme on central molecular processes in the nervous system and on inflammation is presented here.},
  language  = {en}
}