PART 1 Disease forms and animal models of hypophosphatasia 1 Clinical forms and animal models of hypophosphatasia 2 Molecular genetics of hypophosphatasia and phenotype-genotype correlations Etienne MORNET 3 Genetically modified mice for studying TNAP function Sonoko NARISAWA PART 2 Expression and regulation of TNAP in the CNS 4 Tissue-Nonspecific Alkaline Phosphatase in the Developing Brain and in Adult Neurogenesis Herbert Zimmermann and David Langer 5 Rediscovering TNAP in the brain: a major role in regulating the function and development of the cerebral cortex Caroline Fonta, Pascal Barone, Laia Rodriguez Martinez and László Négyessy 6 TNAP in the retina Orsolya Kántor, Dorottya Cserpán, Béla Völgyi, Ákos Lukáts, Zoltán Somogyvári 7 Tissue Non-specific Alkaline Phosphatase (TNAP) in vessels of the brain Barbara Deracinois, Anne-Marie Lenfant, Marie-Pierre Dehouck and Christophe Flahaut PART 3 TNAP functions in the nervous system 8 What can we learn about the neural functions of TNAP from studies on other organs and tissues? José Luis Millán 9 TNAP, an essential player in membrane lipid rafts of neuronal cells Myriam Ermonval, Florence Baychelier, Caroline Fonta 10 Signal transduction pathways of TNAP: molecular network analyses Négyessy L, Györffy B, Hanics J, Bányai M, Ermonval M, Fonta C, Bazsó F 11 Vitamin B-6 Metabolism and Interactions with TNAP Stephen P. Coburn 12 Tetramisole and levamisole suppress neuronal activity independently from their inhibitory action on Tissue Non-Specific Alkaline Phosphatase in mouse cortex Lionel G. Nowak, Benoît Rosay, David Czégé, Caroline Fonta 13 TNAP and Pain Control Sarah E. Street and Nathaniel A. Sowa PART 4 TNAP in neurological disorders 14 Neurological symptoms of Hypophosphatasia Takeshi Taketani 15 Recombinant enzyme replacement therapy in hypophosphatasia Hofmann C, Jakob F, Seefried L, Mentrup B, Graser S, Plotkin H, Girschick HJ, Liese J 16 Neurogenetic Aspects of Hyperphosphatasia in Mabry Syndrome David E.C. Cole and Miles D. Thompson 17 The role of tissue non-specific alkaline phosphatase (TNAP) in Neurodegenerative diseases: Alzheimer’s disease in the focus Katherine AB Kellett & Nigel M Hooper 18 TNAP plays a key role in neural differentiation as well as in neurodegenerative disorders Diaz-Hernandez M, Hernandez F, Miras-Portugal M.T. and Avila J Index
Phosphatases such as TNAP are fundamental in regulating cellular, and consequently numerous body functions. TNAP is a ubiquitous enzyme with a wide spectrum of substrates and specificity regulation at the cellular level and the lack of TNAP activity is a lethal condition. Recent findings of a highly specific regional, laminar and subcellular localization of TNAP in the cerebral cortex indicates that in addition to its metabolic and skeletal functions, TNAP also plays a role in regulating cerebral functions, most probably cognition. In fact, TNAP disturbance could result in complex diseases such as epilepsy, developmental retardation and Alzheimer disease. Available data suggest that, regarding brain functions, TNAP is a potentially important target of clinical research. The proposed book aims to provide an overview of our current understanding of the functions of TNAP in the brain.