TNAP in Central Nervous System: Comparison
Please note this is a comparison between Version 2 by Conner Chen and Version 1 by Candice M. Brown.

Tissue-nonspecific alkaline phosphatase (TNAP) is an ectoenzyme bound to the plasma membranes of numerous cells via a glycosylphosphatidylinositol (GPI) moiety. TNAP is one of many proteins localized to Brain microvascular endothelial cells (BMECs), and is highly abundant in human and rodent cerebral microvessels [33]. There are four alkaline phosphatase (AP) isoenzymes in humans and they include: TNAP, germ cell alkaline phosphatase (GCAP), intestinal alkaline phosphatase (IAP), and placental alkaline phosphatase (PLAP). Although TNAP is ubiquitous in many tissue, it is most highly expressed in bone, liver, intestine, kidney, and brain, while the three other AP isoenzymes are expressed in the tissues for which they are named. TNAP is also highly expressed in cerebral microvessels.

  • brain microvascular endothelial cells
  • cerebral microvessels
  • tissue-nonspecific alkaline phosphatase
  • Alpl
  • TNAP
  • cerebrovascular
Please wait, diff process is still running!

References

  1. Low, M.G. Biochemistry of the glycosyl-phosphatidylinositol membrane protein anchors. Biochem. J. 1987, 244, 1–13.
  2. Low, M.G.; Zilversmit, D.B. Role of phosphatidylinositol in attachment of alkaline phosphatase to membranes. Biochemistry 1980, 19, 3913–3918.
  3. Betz, A.L.; Firth, J.A.; Goldstein, G.W. Polarity of the blood-brain barrier: Distribution of enzymes between the luminal and antiluminal membranes of brain capillary endothelial cells. Brain Res. 1980, 192, 17–28.
  4. Whyte, M.P.; Landt, M.; Ryan, L.M.; Mulivor, R.A.; Henthorn, P.S.; Fedde, K.N.; Mahuren, J.D.; Coburn, S.P. Alkaline phosphatase: Placental and tissue-nonspecific isoenzymes hydrolyze phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5’-phosphate. Substrate accumulation in carriers of hypophosphatasia corrects during pregnancy. J. Clin. Investig. 1995, 95, 1440–1445.
  5. Say, J.; Ciuffi, K.; Furriel, R.P.; Ciancaglini, P.; Leone, F.A. Alkaline phosphatase from rat osseous plates: Purification and biochemical characterization of a soluble form. Biochim. Biophys. Acta BBA Gen. Subj. 1991, 1074, 256–262.
  6. Graser, S.; Liedtke, D.; Jakob, F. TNAP as a New Player in Chronic Inflammatory Conditions and Metabolism. Int. J. Mol. Sci. 2021, 22, 919.
  7. Moore, C.A.; Ward, J.C.; Rivas, M.L.; Magill, H.L.; Whyte, M.P. Infantile hypophosphatasia: Autosomal recessive transmission to two related sibships. Am. J. Med Genet. 1990, 36, 15–22.
  8. Barvencik, F.; Beil, F.T.; Gebauer, M.; Busse, B.; Koehne, T.; Seitz, S.; Zustin, J.; Pogoda, P.; Schinke, T.; Amling, M. Skeletal mineralization defects in adult hypophosphatasia—a clinical and histological analysis. Osteoporos. Int. 2011, 22, 2667–2675.
  9. Fedde, K.N.; Blair, L.; Silverstein, J.; Coburn, S.P.; Ryan, L.M.; Weinstein, R.S.; Waymire, K.; Narisawa, S.; Millan, J.L.; MacGregor, G.R.; et al. Alkaline Phosphatase Knock-Out Mice Recapitulate the Metabolic and Skeletal Defects of Infantile Hypophosphatasia. J. Bone Miner. Res. 1999, 14, 2015–2026.
  10. Whyte, M.P. Hypophosphatasia and the Role of Alkaline Phosphatase in Skeletal Mineralization. Endocr. Rev. 1994, 15, 439–461.
  11. Orimo, H. The Mechanism of Mineralization and the Role of Alkaline Phosphatase in Health and Disease. J. Nippon. Med. Sch. 2010, 77, 4–12.
  12. Harmey, D.; Hessle, L.; Narisawa, S.; Johnson, K.A.; Terkeltaub, R.; Millán, J.L. Concerted Regulation of Inorganic Pyrophosphate and Osteopontin by Akp2, Enpp1, and Ank. Am. J. Pathol. 2004, 164, 1199–1209.
  13. Whyte, M.P. Physiological role of alkaline phosphatase explored in hypophosphatasia. Ann. N. Y. Acad. Sci. 2010, 1192, 190–200.
  14. Waymire, K.G.; Mahuren, J.D.; Jaje, J.M.; Guilarte, T.R.; Coburn, S.P.; MacGregor, G.R. Mice lacking tissue non–specific alkaline phosphatase die from seizures due to defective metabolism of vitamin B-6. Nat. Genet. 1995, 11, 45–51.
  15. Whyte, M.P.; Mahuren, J.D.; Vrabel, L.A.; Coburn, S.P. Markedly increased circulating pyridoxal-5’-phosphate levels in hypophosphatasia. Alkaline phosphatase acts in vitamin B6 metabolism. J. Clin. Investig. 1985, 76, 752–756.
  16. Brun-Heath, I.; Ermonval, M.; Chabrol, E.; Xiao, J.; Palkovits, M.; Lyck, R.; Miller, F.; Couraud, P.-O.; Mornet, E.; Fonta, C. Differential expression of the bone and the liver tissue non-specific alkaline phosphatase isoforms in brain tissues. Cell Tissue Res. 2010, 343, 521–536.
  17. Weiss, M.J.; Ray, K.; Henthorn, P.S.; Lamb, B.; Kadesch, T.; Harris, H. Structure of the human liver/bone/kidney alkaline phosphatase gene. J. Biol. Chem. 1988, 263, 12002–12010.
  18. Toh, Y.; Yamamoto, M.; Endo, H.; Misumi, Y.; Ikehara, Y. Isolation and characterization of a rat liver alkaline phosphatase gene. A single gene with two promoters. JBIC J. Biol. Inorg. Chem. 1989, 182, 231–237.
  19. Studer, M.; Terao, M.; Gianni, M.; Garattini, E. Characterization of a second promoter for the mouse liver/bone/kidney-type alkaline phosphatase gene: Cell and tissue specific expression. Biochem. Biophys. Res. Commun. 1991, 179, 1352–1360.
  20. Matsuura, S.; Kishi, F.; Kajii, T. Characterization of a 5′-flanking region of the human liver/bone/kidney alkaline phosphatase gene: Two kinds of mRNA from a single gene. Biochem. Biophys. Res. Commun. 1990, 168, 993–1000.
  21. Hahnel, A.; Rappolee, D.; Millan, J.; Manes, T.; Ziomek, C.; Theodosiou, N.; Werb, Z.; Pedersen, R.; Schultz, G. Two alkaline phosphatase genes are expressed during early development in the mouse embryo. Development 1990, 110, 555–564.
  22. Kruse, K.; Hanefeld, F.; Kohlschütter, A.; Rosskamp, R.; Gross-Selbeck, G. Hyperphosphatasia with mental retardation. J. Pediatr. 1988, 112, 436–439.
  23. Thompson, M.D.; Nezarati, M.M.; Gillessen-Kaesbach, G.; Meinecke, P.; Mendoza, R.; Mornet, E.; Brun-Heath, I.; Squarcioni, C.P.; Legeai-Mallet, L.; Munnich, A.; et al. Hyperphosphatasia with seizures, neurologic deficit, and characteristic facial features: Five new patients with Mabry syndrome. Am. J. Med. Genet. Part A 2010, 152A, 1661–1669.
  24. Thompson, M.D.; Cole, D.E.; Mabry, C.C. 50 Years Ago in T J P. J. Pediatr. 2020, 222, 97.
  25. Anstrom, J.A.; Brown, W.R.; Moody, D.M.; Thore, C.R.; Challa, V.R.; Block, S.M. Temporal expression pattern of cerebrovascular endothelial cell alkaline phosphatase during human gestation. J. Neuropathol. Exp. Neurol. 2002, 61, 76–84.
  26. Shimizu, N. Histochemical studies on the phosphatase of the nervous system. J. Comp. Neurol. 1950, 93, 201–217.
  27. Fonta, C.; Imbert, M. Vascularization in the Primate Visual Cortex during Development. Cereb. Cortex 2002, 12, 199–211.
  28. Bell, M.A.; Scarrow, W.G. Staining for microvascular alkaline phosphatase in thick celloidin sections of nervous tissue: Morphometric and pathological applications. Microvasc. Res. 1984, 27, 189–203.
  29. Norman, M.G.; O’Kusky, J.R. The growth and development of microvasculature in human cerebral cortex. J. Neuropathol. Exp. Neurol. 1986, 45, 222–232.
  30. Latker, C.H.; Shinowara, N.L.; Miller, J.C.; Rapoport, S.I. Differential localization of alkaline phosphatase in barrier tissues of the frog and rat nervous systems: A cytochemical and biochemical study. J. Comp. Neurol. 1987, 264, 291–302.
  31. Mizuguchi, H.; Hashioka, Y.; Utoguchi, N.; Kubo, K.; Nakagawa, S.; Mayumi, T. A Comparison of Drug Transport through Cultured Monolayers of Bovine Brain Capillary and Bovine Aortic Endothelial Cells. Biol. Pharm. Bull. 1994, 17, 1385–1390.
  32. Vorbrodt, A.W.; Lossinsky, A.S.; Wisniewski, H.M. Localization of Alkaline Phosphatase Activity in Endothelia of Developing and Mature Mouse Blood-Brain Barrier. Dev. Neurosci. 1986, 8, 1–13.
  33. Mayahara, H.; Hirano, H.; Saito, T.; Ogawa, K. The new lead citrate method for the ultracytochemical demonstration of activity of non-specific alkaline phosphatase (orthophosphoric monoester phosphohydrolase). Histochem. Cell Biol. 1967, 11, 88–96.
  34. Mori, S.; Nagano, M. Electron-microscopic cytochemistry of alkaline-phosphatase activity in endothelium, pericytes and oligodendrocytes in the rat brain. Histochem. Cell Biol. 1985, 82, 225–231.
  35. Ovtscharoff, W. Ultracytochemische Lokalisierung der alkalischen Phosphatase im Cortex cerebri bei neugeborenen Ratten. Histochem. Cell Biol. 1973, 37, 93–95.
  36. Deracinois, B.; Duban-Deweer, S.; Pottiez, G.; Cecchelli, R.; Karamanos, Y.; Flahaut, C. TNAP and EHD1 Are Over-Expressed in Bovine Brain Capillary Endothelial Cells after the Re-Induction of Blood-Brain Barrier Properties. PLoS ONE 2012, 7, e48428.
  37. Meyer, J.; Rauh, J.; Galla, H.-J. The Susceptibility of Cerebral Endothelial Cells to Astroglial Induction of Blood-Brain Barrier Enzymes Depends on Their Proliferative State. J. Neurochem. 1991, 57, 1971–1977.
  38. Rauh, J.; Meyer, J.; Beuckmann, C.; Galla, H.-J. Chapter 18: Development of an in vitro cell culture system to mimic the blood-brain barrier. Progress Brain Res. 1992, 91, 117–121.
  39. Tio, S.; Deenen, M.; Marani, E. Astrocyte-mediated induction of alkaline phosphatase activity in human umbilical cord vein endothelium: An in vitro model. Eur. J. Morphol. 1990, 28, 289–300.
  40. Ohlebusch, B.; Borst, A.; Frankenbach, T.; Klopocki, E.; Jakob, F.; Liedtke, D.; Graser, S. Investigation of alpl expression and Tnap-activity in zebrafish implies conserved functions during skeletal and neuronal development. Sci. Rep. 2020, 10, 1–16.
  41. McComb, R.B.; Bowers, G.N., Jr.; Posen, S. Alkaline Phosphatase; Springer Science and Business Media LLC: Berlin, Germany, 1979; 986p.
  42. Friede, R.L. A quantitative mapping of alkaline phosphatase in the brain of the rhesus monkey. J. Neurochem. 1966, 13, 197–203.
  43. Negyessy, L.; Xiao, J.; Kántor, O.; Kovacs, G.G.; Palkovits, M.; Doczi, T.; Renaud, L.; Baksa, G.; Glasz, T.; Ashaber, M.; et al. Layer-specific activity of tissue non-specific alkaline phosphatase in the human neocortex. Neuroscience 2011, 172, 406–418.
  44. Liu, J.; Nam, H.K.; Campbell, C.; Gasque, K.C.D.S.; Millán, J.L.; Hatch, N.E. Tissue-nonspecific alkaline phosphatase deficiency causes abnormal craniofacial bone development in the Alpl−/− mouse model of infantile hypophosphatasia. Bone 2014, 67, 81–94.
  45. Liedtke, D.; Hofmann, C.; Jakob, F.; Klopocki, E.; Graser, S. Tissue-Nonspecific Alkaline Phosphatase—A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease. Biomolecules 2020, 10, 1648.
  46. Sebastián-Serrano, Á.; De Diego-García, L.; Henshall, D.C.; Engel, T.; Diaz-Hernandez, M. Haploinsufficient TNAP Mice Display Decreased Extracellular ATP Levels and Expression of Pannexin-1 Channels. Front. Pharmacol. 2018, 9.
  47. Gámez-Belmonte, R.; Tena-Garitaonaindia, M.; Hernández-Chirlaque, C.; Córdova, S.; Ceacero-Heras, D.; De Medina, F.S.; Martínez-Augustin, O. Deficiency in Tissue Non-Specific Alkaline Phosphatase Leads to Steatohepatitis in Mice Fed a High Fat Diet Similar to That Produced by a Methionine and Choline Deficient Diet. Int. J. Mol. Sci. 2020, 22, 51.
  48. Hernández-Chirlaque, C.; Gámez-Belmonte, R.; Ocón, B.; Martínez-Moya, P.; Wirtz, S.; de Medina, F.S.; Martínez-Augustin, O. Tissue Non-specific Alkaline Phosphatase Expression is Needed for the Full Stimulation of T Cells and T Cell-Dependent Colitis. J. Crohns Colitis 2016, 11, 857–870.
  49. Yamamoto, S.; Orimo, H.; Matsumoto, T.; Iijima, O.; Narisawa, S.; Maeda, T.; Millán, J.L.; Shimada, T. Prolonged survival and phenotypic correction of Akp2−/− hypophosphatasia mice by lentiviral gene therapy. J. Bone Miner. Res. 2010, 26, 135–142.
  50. Nam, H.K.; Vesela, I.; Schutte, S.D.; Hatch, N.E. Viral delivery of tissue nonspecific alkaline phosphatase diminishes craniosynostosis in one of two FGFR2C342Y/+ mouse models of Crouzon syndrome. PLoS ONE 2020, 15, e0234073.
  51. Arnò, B.; Galli, F.; Roostalu, U.; Aldeiri, B.M.; Miyake, T.; Albertini, A.; Bragg, L.; Prehar, S.; McDermott, J.C.; Cartwright, E.J.; et al. TNAP limits TGF-β-dependent cardiac and skeletal muscle fibrosis by inactivating the SMAD2/3 transcription factors. J. Cell Sci. 2019, 132, jcs.234948.
  52. Sheen, C.R.; Kuss, P.; Narisawa, S.; Yadav, M.C.; Nigro, J.; Wang, W.; Chhea, T.N.; Sergienko, E.A.; Kapoor, K.; Jackson, M.R.; et al. Pathophysiological Role of Vascular Smooth Muscle Alkaline Phosphatase in Medial Artery Calcification. J. Bone Miner. Res. 2015, 30, 824–836.
  53. Savinov, A.Y.; Salehi, M.; Yadav, M.C.; Radichev, I.A.; Millán, J.L.; Savinova, O.V. Transgenic Overexpression of Tissue-Nonspecific Alkaline Phosphatase (TNAP) in Vascular Endothelium Results in Generalized Arterial Calcification. J. Am. Hear. Assoc. 2015, 4, e002499.
  54. Rodionov, R.N.; Begmatov, H.; Jarzebska, N.; Patel, K.; Mills, M.T.; Ghani, Z.; Khakshour, D.; Tamboli, P.; Patel, M.N.; Abdalla, M.; et al. Homoarginine Supplementation Prevents Left Ventricular Dilatation and Preserves Systolic Function in a Model of Coronary Artery Disease. J. Am. Hear. Assoc. 2019, 8, e012486.
  55. Romanelli, F.; Corbo, A.; Salehi, M.; Yadav, M.C.; Salman, S.; Petrosian, D.; Rashidbaigi, O.J.; Chait, J.; Kuruvilla, J.; Plummer, M.; et al. Overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelial cells accelerates coronary artery disease in a mouse model of familial hypercholesterolemia. PLoS ONE 2017, 12, e0186426.
  56. Brichacek, A.L.; Benkovic, S.A.; Chakraborty, S.; Nwafor, D.C.; Wang, W.; Jun, S.; Dakhlallah, D.; Geldenhuys, W.J.; Pinkerton, A.B.; Millán, J.L.; et al. Systemic inhibition of tissue-nonspecific alkaline phosphatase alters the brain-immune axis in experimental sepsis. Sci. Rep. 2019, 9, 1–19.
  57. Foster, B.; Kuss, P.; Yadav, M.; Kolli, T.; Narisawa, S.; Lukashova, L.; Cory, E.; Sah, R.; Somerman, M.; Millán, J. Conditional Alpl Ablation Phenocopies Dental Defects of Hypophosphatasia. J. Dent. Res. 2016, 96, 81–91.
  58. Nwafor, D.C.; Brichacek, A.L.; Wang, W.; Bidwai, N.; Lilly, C.L.; Millan, J.; Brown, C.M. Brain endothelial cell tissue-nonspecific alkaline phosphatase (TNAP) activity promotes maintenance of barrier integrity via the ROCK pathway. bioRxiv 2021.
  59. Alva, J.A.; Zovein, A.C.; Monvoisin, A.; Murphy, T.; Salazar, A.; Harvey, N.L.; Carmeliet, P.; Iruela-Arispe, M.L. VE-Cadherin-Cre-recombinase transgenic mouse: A tool for lineage analysis and gene deletion in endothelial cells. Dev. Dyn. 2006, 235, 759–767.
  60. Assmann, J.C.; Körbelin, J.; Schwaninger, M. Genetic manipulation of brain endothelial cells in vivo. Biochim. Biophys. Acta BBA Mol. Basis Dis. 2016, 1862, 381–394.
  61. Rufo, M.B.; Fishman, W.H. l-Homoarginine, a specific inhibitor of liver-type alkaline phosphatase, applied to the recognition of liver-type enzyme activity in rat intestine. J. Histochem. Cytochem. 1972, 20, 336–343.
  62. Kozlenkov, A.; Le Du, M.H.; Cuniasse, P.; Ny, T.; Hoylaerts, M.F.; Millán, J.L. Residues Determining the Binding Specificity of Uncompetitive Inhibitors to Tissue-Nonspecific Alkaline Phosphatase. J. Bone Miner. Res. 2004, 19, 1862–1872.
  63. Deracinois, B.; Lenfant, A.-M.; Dehouck, M.-P.; Flahaut, C. Tissue Non-specific Alkaline Phosphatase (TNAP) in Vessels of the Brain. Subcell. Biochem. 2015, 76, 125–151.
  64. Dahl, R.; Sergienko, E.A.; Su, Y.; Mostofi, Y.S.; Yang, L.; Simão, A.M.; Narisawa, S.; Brown, B.; Mangravita-Novo, A.; Vicchiarelli, M.; et al. Discovery and Validation of a Series of Aryl Sulfonamides as Selective Inhibitors of Tissue-Nonspecific Alkaline Phosphatase (TNAP). J. Med. Chem. 2009, 52, 6919–6925.
  65. Nakamura, T.; Nakamura-Takahashi, A.; Kasahara, M.; Yamaguchi, A.; Azuma, T. Tissue-nonspecific alkaline phosphatase promotes the osteogenic differentiation of osteoprogenitor cells. Biochem. Biophys. Res. Commun. 2020, 524, 702–709.
  66. Pinkerton, A.B.; Sergienko, E.; Bravo, Y.; Dahl, R.; Ma, C.-T.; Sun, Q.; Jackson, M.R.; Cosford, N.D.P.; Millán, J.L. Discovery of 5-((5-chloro-2-methoxyphenyl)sulfonamido)nicotinamide (SBI-425), a potent and orally bioavailable tissue-nonspecific alkaline phosphatase (TNAP) inhibitor. Bioorg. Med. Chem. Lett. 2018, 28, 31–34.
  67. Genest, F.; Rak, D.; Petryk, A.; Seefried, L. Physical Function and Health-Related Quality of Life in Adults Treated With Asfotase Alfa for Pediatric-Onset Hypophosphatasia. JBMR Plus 2020, 4.
  68. Kishnani, P.S.; Rockman-Greenberg, C.; Rauch, F.; Bhatti, M.T.; Moseley, S.; Denker, A.E.; Watsky, E.; Whyte, M.P. Five-year efficacy and safety of asfotase alfa therapy for adults and adolescents with hypophosphatasia. Bone 2019, 121, 149–162.
  69. Whyte, M.P.; Simmons, J.H.; Moseley, S.; Fujita, K.P.; Bishop, N.; Salman, N.J.; Taylor, J.; Phillips, D.; McGinn, M.; McAlister, W.H. Asfotase alfa for infants and young children with hypophosphatasia: 7 year outcomes of a single-arm, open-label, phase 2 extension trial. Lancet Diabetes Endocrinol. 2019, 7, 93–105.
  70. Pickkers, P.; Snellen, F.; Rogiers, P.; Bakker, J.; Jorens, P.; Meulenbelt, J.; Spapen, H.; Tulleken, J.E.; Lins, R.; Ramael, S.; et al. Clinical pharmacology of exogenously administered alkaline phosphatase. Eur. J. Clin. Pharmacol. 2009, 65, 393–402.
  71. Heemskerk, S.; Masereeuw, R.; Moesker, O.; Bouw, M.P.W.J.M.; Van Der Hoeven, J.G.; Peters, W.H.M.; Russel, F.G.M.; Pickkers, P. Alkaline phosphatase treatment improves renal function in severe sepsis or septic shock patients. Crit. Care Med. 2009, 37, 417-e1.
  72. Bender, B.; Baranyi, M.; Kerekes, A.; Bodrogi, L.; Brands, R.; Uhrin, P.; Bösze, Z. Recombinant Human Tissue Non-Specific Alkaline Phosphatase Successfully Counteracts Lipopolysaccharide Induced Sepsis in Mice. Physiol. Res. 2015, 64, 731–738.
  73. Pickkers, P.; Heemskerk, S.; Schouten, J.; Laterre, P.-F.; Vincent, J.-L.; Beishuizen, A.; Jorens, P.G.; Spapen, H.; Bulitta, M.; Peters, W.H.; et al. Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: A prospective randomized double-blind placebo-controlled trial. Crit. Care 2012, 16, R14.
  74. Lukas, M.; Drastich, P.; Konecny, M.; Gionchetti, P.; Urban, O.; Cantoni, F.; Bortlik, M.; Duricova, D.; Bulitta, M. Exogenous alkaline phosphatase for the treatment of patients with moderate to severe ulcerative colitis. Inflamm. Bowel Dis. 2010, 16, 1180–1186.
  75. Engelmann, C.; Adebayo, D.; Oria, M.; De Chiara, F.; Novelli, S.; Habtesion, A.; Davies, N.; Andreola, F.; Jalan, R. Recombinant Alkaline Phosphatase Prevents Acute on Chronic Liver Failure. Sci. Rep. 2020, 10, 1–13.
  76. Peters, E.; Ergin, B.; Kandil, A.; Gurel-Gurevin, E.; Van Elsas, A.; Masereeuw, R.; Pickkers, P.; Ince, C. Effects of a human recombinant alkaline phosphatase on renal hemodynamics, oxygenation and inflammation in two models of acute kidney injury. Toxicol. Appl. Pharmacol. 2016, 313, 88–96.
  77. Juschten, J.; for the BASIC study investigators; Ingelse, S.A.; Bos, L.D.J.; Girbes, A.R.J.; Juffermans, N.P.; Van Der Poll, T.; Schultz, M.J.; Tuinman, P.R. Alkaline phosphatase in pulmonary inflammation—A translational study in ventilated critically ill patients and rats. Intensive Care Med. Exp. 2020, 8, 1–14.
  78. Pickkers, P.; Mehta, R.L.; Murray, P.T.; Joannidis, M.; Molitoris, B.A.; Kellum, J.A.; Bachler, M.; Hoste, E.A.J.; Hoiting, O.; Krell, K.; et al. Effect of Human Recombinant Alkaline Phosphatase on 7-Day Creatinine Clearance in Patients With Sepsis-Associated Acute Kidney Injury. JAMA 2018, 320, 1998–2009.
  79. Vanlandewijck, M.; He, L.; Mäe, M.A.; Andrae, J.; Ando, K.; Del Gaudio, F.; Nahar, K.; Lebouvier, T.; Laviña, B.; Gouveia, L.; et al. A molecular atlas of cell types and zonation in the brain vasculature. Nat. Cell Biol. 2018, 554, 475–480.
  80. Yang, A.C.; Stevens, M.Y.; Chen, M.B.; Lee, D.P.; Stähli, D.; Gate, D.; Contrepois, K.; Chen, W.; Iram, T.; Zhang, L.; et al. Physiological blood–brain transport is impaired with age by a shift in transcytosis. Nat. Cell Biol. 2020, 583, 425–430.
  81. Beuckmann, C.; Hellwig, S.; Galla, H.-J. Induction of the Blood/Brain-Barrier-Associated Enzyme Alkaline Phosphatase in Endothelial Cells from Cerebral Capillaries is Mediated Via cAMP. JBIC J. Biol. Inorg. Chem. 1995, 229, 641–644.
  82. Roux, F.; Durieu-Trautmann, O.; Chaverot, N.; Claire, M.; Mailly, P.; Bourre, J.-M.; Strosberg, A.D.; Couraud, P.-O. Regulation of gamma-glutamyl transpeptidase and alkaline phosphatase activities in immortalized rat brain microvessel endothelial cells. J. Cell. Physiol. 1994, 159, 101–113.
  83. Shibuya, M.; Hirai, S.; Seto, M.; Satoh, S.-I.; Ohtomo, E. Effects of fasudil in acute ischemic stroke: Results of a prospective placebo-controlled double-blind trial. J. Neurol. Sci. 2005, 238, 31–39.
  84. Fukuta, T.; Asai, T.; Yanagida, Y.; Namba, M.; Koide, H.; Shimizu, K.; Oku, N. Combination therapy with liposomal neuroprotectants and tissue plasminogen activator for treatment of ischemic stroke. FASEB J. 2017, 31, 1879–1890.
  85. Liu, K.; Li, Z.; Wu, T.; Ding, S. Role of Rho Kinase in Microvascular Damage Following Cerebral Ischemia Reperfusion in Rats. Int. J. Mol. Sci. 2011, 12, 1222–1231.
  86. Jianjun, Z.; Baochun, Z.; Limei, M.; Lijun, L. Exploring the beneficial role of ROCK inhibitors in sepsis-induced cerebral and cognitive injury in rats. Fundam. Clin. Pharmacol. 2021.
  87. Adams, S.E.; Melnykovych, G. Synergistic stimulation of alkaline phosphatase activity in bovine aortic endothelial cells grown in the presence of retinoids and glucocorticoids. J. Cell. Physiol. 1985, 124, 120–124.
  88. Nakazato, H.; Deguchi, M.; Fujimoto, M.; Fukushima, H. Alkaline phosphatase expression in cultured endothelial cells of aorta and brain micro vessels: Induction by interleukin-6-type cytokines and suppression by transforming growth factor betas. Life Sci. 1997, 61, 2065–2072.
  89. Romero, C.R.; Herzig, D.S.; Etogo, A.; Nunez, J.; Mahmoudizad, R.; Fang, G.; Murphey, E.D.; Toliver-Kinsky, T.; Sherwood, E.R. The role of interferon-γ in the pathogenesis of acute intra-abdominal sepsis. J. Leukoc. Biol. 2010, 88, 725–735.
  90. Varatharaj, A.; Galea, I. The blood-brain barrier in systemic inflammation. Brain Behav. Immun. 2017, 60, 1–12.
  91. Brown, W.R.; Moody, D.M.; Thore, C.R.; Challa, V.R.; Anstrom, J.A. Vascular dementia in leukoaraiosis may be a consequence of capillary loss not only in the lesions, but in normal-appearing white matter and cortex as well. J. Neurol. Sci. 2007, 257, 62–66.
  92. Goncharov, N.V.; Nadeev, A.D.; Jenkins, R.O.; Avdonin, P.V. Markers and Biomarkers of Endothelium: When Something Is Rotten in the State. Oxid. Med. Cell. Longev. 2017, 2017, 1–27.
  93. Nwafor, D.C.; Brichacek, A.L.; Mohammad, A.S.; Griffith, J.; Lucke-Wold, B.P.; Benkovic, S.A.; Geldenhuys, W.J.; Lockman, P.R.; Brown, C.M. Targeting the Blood-Brain Barrier to Prevent Sepsis-Associated Cognitive Impairment. J. Central Nerv. Syst. Dis. 2019, 11.
  94. Nwafor, D.C.; Chakraborty, S.; Brichacek, A.L.; Jun, S.; Gambill, C.A.; Wang, W.; Engler-Chiurazzi, E.B.; Dakhlallah, D.; Pinkerton, A.B.; Millán, J.L.; et al. Loss of tissue-nonspecific alkaline phosphatase (TNAP) enzyme activity in cerebral microvessels is coupled to persistent neuroinflammation and behavioral deficits in late sepsis. Brain Behav. Immun. 2020, 84, 115–131.
  95. Iwashyna, T.J.; Ely, E.W.; Smith, D.M.; Langa, K.M. Long-term Cognitive Impairment and Functional Disability Among Survivors of Severe Sepsis. JAMA 2010, 304, 1787–1794.
  96. Andonegui, G.; Zelinski, E.L.; Schubert, C.L.; Knight, D.; Craig, L.A.; Winston, B.W.; Spanswick, S.C.; Petri, B.; Jenne, C.N.; Sutherland, J.C.; et al. Targeting inflammatory monocytes in sepsis-associated encephalopathy and long-term cognitive impairment. JCI Insight 2018, 3.
  97. Chavan, S.S.; Huerta, P.T.; Robbiati, S.; Valdes-Ferrer, S.I.; Ochani, M.; Dancho, M.; Frankfurt, M.; Volpe, B.T.; Tracey, K.J.; Diamond, B. HMGB1 Mediates Cognitive Impairment in Sepsis Survivors. Mol. Med. 2012, 18, 930–937.
  98. Barone, F.C.; Arvin, B.; White, R.F.; Miller, A.R.; Webb, C.L.; Willette, R.N.; Lysko, P.G.; Feuerstein, G.Z. Tumor Necrosis Factor-α. Stroke 1997, 28, 1233–1244.
  99. Michie, H.R.; Manogue, K.R.; Spriggs, D.R.; Revhaug, A.; O’Dwyer, S.; Dinarello, C.A.; Cerami, A.; Wolff, S.M.; Wilmore, D.W. Detection of Circulating Tumor Necrosis Factor after Endotoxin Administration. N. Engl. J. Med. 1988, 318, 1481–1486.
  100. Yilmaz, G.; Arumugam, T.V.; Stokes, K.Y.; Granger, D.N. Role of T Lymphocytes and Interferon-γ in Ischemic Stroke. Circulation 2006, 113, 2105–2112.
  101. Colton, C.A.; Wilcock, D.M.; Wink, D.A.; Davis, J.; Van Nostrand, W.E.; Vitek, M.P. The Effects of NOS2 Gene Deletion on Mice Expressing Mutated Human AβPP. J. Alzheimer’s Dis. 2008, 15, 571–587.
  102. Wilcock, D.M.; Lewis, M.R.; Van Nostrand, W.E.; Davis, J.; Previti, M.L.; Gharkholonarehe, N.; Vitek, M.P.; Colton, C.A. Progression of Amyloid Pathology to Alzheimer’s Disease Pathology in an Amyloid Precursor Protein Transgenic Mouse Model by Removal of Nitric Oxide Synthase 2. J. Neurosci. 2008, 28, 1537–1545.
  103. Nwafor, D.C.; Chakraborty, S.; Jun, S.; Brichacek, A.L.; Dransfeld, M.; Gemoets, D.E.; Dakhlallah, D.; Brown, C.M. Disruption of metabolic, sleep, and sensorimotor functional outcomes in a female transgenic mouse model of Alzheimer’s disease. Behav. Brain Res. 2021, 398, 112983.
  104. Díaz-Hernández, M.; Gómez-Ramos, A.; Rubio, A.; Gómez-Villafuertes, R.; Naranjo, J.R.; Miras-Portugal, M.T.; Avila, J. Tissue-nonspecific Alkaline Phosphatase Promotes the Neurotoxicity Effect of Extracellular Tau. J. Biol. Chem. 2010, 285, 32539–32548.
  105. Banks, W.A.; Reed, M.J.; Logsdon, A.F.; Rhea, E.M.; Erickson, M.A. Healthy aging and the blood–brain barrier. Nat. Aging 2021, 1, 243–254.
  106. Yousef, H.; Czupalla, C.J.; Lee, D.; Chen, M.B.; Burke, A.N.; Zera, K.A.; Zandstra, J.; Berber, E.; Lehallier, B.; Mathur, V.; et al. Aged blood impairs hippocampal neural precursor activity and activates microglia via brain endothelial cell VCAM1. Nat. Med. 2019, 25, 988–1000.
  107. Chen, M.B.; Yang, A.C.; Yousef, H.; Lee, D.; Chen, W.; Schaum, N.; Lehallier, B.; Quake, S.R.; Wyss-Coray, T. Brain Endothelial Cells Are Exquisite Sensors of Age-Related Circulatory Cues. Cell Rep. 2020, 30, 4418–4432.
More
Video Production Service