Transport mechanisms at the blood-cerebrospinal-fluid barrier: Role of megalin (LRP2)

Recent Patents on Endocrine, Metabolic and Immune Drug Discovery

Volumn 4, Issue 3, 2010, Pages 190-205

  Spuch, Carlos ^a   Navarro, Carmen ^a  

^a UNIVERSITY HOSPITAL COMPLEX OF VIGO   (Spain)

Author keywords

Alzheimer's disease; Amyloid; Blood brain barrier; Blood CSF barrier; Clearance; Drug delivery; IGF; LRP 1; LRP2; Megalin

Indexed keywords

AMYLOID BETA PROTEIN ANTIBODY; AMYLOID BETA PROTEIN IMMUNOGLOBULIN G ANTIBODY; APOLIPOPROTEIN A; APOLIPOPROTEIN E; APOLIPOPROTEIN M; APROTININ; BETA2 GLYCOPROTEIN 1; CENTRAL STIMULANT AGENT; CLUSTERIN; IMMUNOGLOBULIN; INSULIN; LEPTIN; LEVODOPA; LIPOPROTEIN RECEPTOR; LOW DENSITY LIPOPROTEIN RECEPTOR; MEGALIN; NEUROTRANSMITTER; PARATHYROID HORMONE; PLASMINOGEN ACTIVATOR INHIBITOR 1; POLYMYXIN B; PREALBUMIN; RECOMBINANT PROTEIN; RETINOL; RETINOL BINDING PROTEIN; SOMATOMEDIN C; THYROGLOBULIN; TRICHOSTATIN A; UNCLASSIFIED DRUG; UNINDEXED DRUG; UROKINASE; VITAMIN D BINDING PROTEIN;

ALZHEIMER DISEASE; ARTICLE; BLOOD BRAIN BARRIER; BRAIN DISEASE; CELL MIGRATION; CENTRAL NERVOUS SYSTEM; CEREBROSPINAL FLUID; CHOROID PLEXUS; CLINICAL RESEARCH; CLINICAL TRIAL; COW; CYTOPLASM; DRUG DELIVERY SYSTEM; DRUG DESIGN; DRUG MANUFACTURE; DRUG PENETRATION; DRUG TRANSPORT; ENDOCYTOSIS; HUMAN; IN VITRO STUDY; IN VIVO STUDY; NEUROPROTECTION; NONHUMAN; PARKINSON DISEASE; PATENT; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN TRANSPORT; RABBIT; SWINE;

EID: 78649374892     PISSN: 18722148     EISSN: None     Source Type: Journal    
DOI: 10.2174/1872214811004030190     Document Type: Article

References (179)

1. Neuwelt E, Abbott NJ, Abrey L, Banks WA, Blakley B, Davis T, et al. Strategies to advance translational research into brain barriers. Lancet Neurol 2008; 7: 84-96.
2. Abbott NJ, Ronnback L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 2006; 7(1): 41-53.
3. Zlokovic BV, Neurovascular mechanisms of Alzheimer's neurodegeneration. Trens Neurosci 2005; 28: 202-8.
4. Kniesel U, Wolburg H. Tight junctions of the blood-brain barrier. Cell Mol Neurobiol 2000; 20(1): 57-76.
5. Zlokovic BV. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 2008; 57(2):178-201.
6. Brown PD, Davies SL, Speake T, Millar ID. Molecular mechanism of cerebrospinal fluid production. Neuroscience 2004; 129: 957-70.
7. Vandenabeele F, Creemers J, Lambrichts I. Ultrastructure of the human spinal arachnoid mater and dura mater. J Anat 1996; 189: 417-30.
8. Nischwitz V, Berthele A, Michalke B. Speciation analysis of selected metals and determination of their total contents in paired serum and cerebrospinal fluid samples: An approach to investigate the permeability of the human blood-cerebrospinal fluid-barrier. Anal Chim Acta 2008; 627: 258-69.
9. Jeong SM, Hahm KD, Shin JW, Leem JG, Lee C, Han SM. Changes in magnesium concentration in the serum and cerebrospinal fluid of neuropathic rats. Acta Anaesthesiol Scand 2006; 50: 211-6.
10. Bernacki J, Dobrowolska A, Nierwiska K, Maecki A. Physiology and pharmacological role of the blood-brain barrier. Pharmacol Rep 2008; 60: 600-22.
11. Nadal A, Fuentes E, Pastor J, McNaughton PA. Plasma albumin is a potent trigger of calcium signals and DNA synthesis in astrocytes. Proc Natl Acad Sci USA 1995; 92: 1426-30.
12. Gingrich MB, Junge CE, Lyuboslavsky P, Traynellis SF. Potentiation of NMDA receptor function by the serine protease thrombin. J Neurosci 2000; 20: 4582-95.
13. Lim DA, Huang YC Alvarez-Buylla A. The adult neural stem cell niche: Lessons for future neural cell replacement strategies. Neurosurg Clin N Am 2007; 18: 81-92.
14. Wolburg S, Noell A, Mack K, Wolburg-Buchholz, Fallier-Becker P. Brain endothelial cells and the glio-vascular complex. Cell Tissue Res 2009; 335: 75-96.
15. Carvey PM, Hendey B, Monahan AJ. The blood brain barrier in neurodegenarive disease: A rhetorical perspective. J Neurochem 2009; 111(2): 291-314.
16. Morgan EH, Moos T. Mechanism and developmental changes in iron transport across the blood-brain barrier. Dev Neurosci 2002; 24(2-3): 106-13.
17. Dietrich MO, Spuch C, Antequera D, Rodal I, de Yebenes JG, Molina JA, et al. Megalin mediates the transport of leptin across the blood-CSF barrier. Neurobiol Aging 2008; 29(56): 902-12.
18. Bell RD, Zlokovic BV. Neurovascular mechanisms and blood-brain-barrier disorder in Alzheimer's disease. Acta Neuropathol 2009; 118(1): 103-13.
19. Carro E, Spuch C, Trejo JL, Antequera D, Torres-Aleman I. Choroid plexus megalin is involved in neuroprotection by serum insulin-like growth factor I. J Neurosci 2005; 25(47): 10884-93.
20. Jones AR, Shusta EV. Blood-brain barrier transport of therapeutics via receptor-mediation. Pharm Res 2007; 24(9): 1759-71.
21. Torres-Aleman I. Targeting insulin-like growth factor-1 to treat Alzheimer's disease. Expert Opin Ther Targets 2007; 11(12): 1535-42.
22. Carro E, Trejo JL, Spuch C, Bohl D, Heard JM, Torres-Aleman I. Blockade of the insulin growth factor I receptor in the choroid plexus originates Alzheimer's-like neuropathology in rodents: New cues into the human disease? Neurobiol Aging 2006; 27(11): 1618-31.
23. Deane R, Bell RD, Sagare A, Zlokovic BV. Clearance of amyloid-beta peptide across the blood-brain barrier: Implication for therapies in Alzheimer's disease. CNS Neurol Disord Drug Targets 2009; 8(1): 16-30.
24. Zlokovic, B.V., Deane, R. Low-density lipoprotein 2 clears amyloid-beta peptide a cross the blood-brain barrier via apolipoprotein J. US20090156525 (2009).
25. Dickson PW, Aldred AR, Marley PD, Bannister D, Schreiber G. Rat choroid plexus specializes in the synthesis and secretion of transthyretin (prealbumin). Regulation of transthyretin synthesis in choroid plexus is independent from that in the liver. J Biol Chem 1986; 261: 3475-8.
26. Nilsson C, Lindvall-Axelsson M, Owman CH. Neuroendocrine regulatory mechanisms in the choroid plexus-cerebrospinal fluid system. Brain Res Rev 1992; 17: 109-38.
27. Chodobski A, Szmydynger-Chodobska J. Choroid plexus: Target for polypeptides and site of their synthesis. Microsc Res Tech 2001; 52: 865-82.
28. Chodobski A, Wojcik BE, Loh YP, Dodd KA, Szmydynger-Chodobska J, Johanson CE, et al. Vasopressin gene expression in rat choroids plexus. Adv Exp Med Biol 1998; 449: 59-65.
29. Quan N, Whiteside M, Herkenham M. Time course and localization patterns of interleukin-1 messenger RNA expression in brain and pituitary after peripheral administration of lypopolysaccharide. Neuroscience 1998; 83: 281-93.
30. Brochu S, Olivier M, Rivest S. Neuronal activity and transcription of proinflammatory cytokines, I B, and iNOS in the mouse brain during acute endotoxemia and chronic infection with Tripanosoma brucei. J Neurosci Res 1999; 57: 801-16.
31. Tarlow MJ, Jenkins R, Comis SD, Osborne MP, Stephens S, Stanley P, et al. Ependymal cells of the choroid plexus express tumour necrosis factor-α. Neuropatol Appl Neurobiol 1993; 19: 324-8.
32. Bondy C, Werner H, Roerts CJ, LeRoith D. Cellular pattern of type-I insuline-like growth factor receptor gene expression during maturation of the rat brain: Comparison with insuline-like growth factors I and II. Neuroscience 1992; 46: 909-23.
33. Timmusk T, Mudo G, Metsis M, Belluardo N. Expression of mRNAs for neurotrophins and their receptors in the rat choroid plexus and dura mater. Neuroreport 1995; 6: 1997-2000.
34. Unsicker K, Flanders KC, Cissel DS, Lafyatis R, Sporn MB. Transforming growth factor -ß isoforms in the adult rat central and peripheral nervous system. Neuroscience 1991; 44: 613-25.
35. Naito S, Chang L, Pettigrew K, Ishihara S, Brightman M. Conditions that may determine blood vessel phenotype in tissues grafted to brain. Exp Neurol 1995; 134: 230-43.
36. Tsutsumi M, Skiner MK, Sanders-Bush E. Transferrin gene expression and synthesis by cultured choroid plexus epithelial cells. Regulation by serotonin and cyclic adenosine 3.5.monophosphate. J Biol Chem 1989; 264: 9626-31.
37. Dickson PW, Aldred AR, Marley PD, Bannister D, Schreiber G. Rat choroid plexus specializes in the synthesis and secretion of transthyretin (prealbumin). Regulation of transthyretin synthesis in choroid plexus is independent from that in the liver. J Biol Chem 1986; 261: 3475-8.
38. Antequera D, Vargas T, Ugalde C, Spuch C, Molina JA, Ferrer I, et al. Cytoplasmic gelsolin increases mitochondrial activity and reduces Abeta burden in a mouse model of Alzheimer's disease. Neurobiol Dis 2009; 36(1): 42-50.
39. Chodobski A, Loh YP, Corsetti S, Szmydynger-Chodobska J, Johanson CE, Lim YP, et al. The presence of arginine vasopressin and its mRNA in rat choroids plexus epithelium. Brain Res Mol Brain Res 1997; 48: 67-72.
40. Pardridge WM. Biopharmaceutical drug targeting to the brain. J Drug Target 2010; 18(3): 157-67.
41. Pardridge WM. CNS drug design based on principles of blood-brain barrier transport. J. Neurochem 1998; 70: 1781-92.
42. Nelson, T., Quattrone, A., Alkdom, D. Artificial Low density lipoproteins carriers for transport of substances across of the blood brain barrier. US20080160094 (2008).
43. Deli MA, Abraham CS, Kataoka Y, Niwa M. Permeability studies on in vitro blood-brain barrier models: Physiology, pathology, and pharmacology. Cell Mol Neurobiol 2005; 25: 59-127.
44. Baehr C, Reichel V, Fricker G. Choroid plexus epithelial monolayers, a cell culture model from porcine brain. Cerebrospinal Fluid Res 2006; 3: 1-14.
45. Strazielle N, Gershi-Egea JF. Demonstration of a coupled metabolism-efflux process at the choroid plexus as a mechanism of brain protection towards xenobiotics. J Neurosci 1999; 19: 6275-89.
46. Rubin LL, Hall DE, Porter S, Barbu K, Cannon C, Homer HC, et al. A cell culture model of the blood brain barrier. J Cell Biol 1991; 115: 1725-35.
47. Zenker D, Begley D, Bratzke H, Rübsamen-Waigmann H, von Briesen H. Human blood derived macrophages enhance barrier function of cultured brain capillary endothelial cells. J Physiol 2003; 551: 1023-32.
48. Cucullo L, Couraud PO, Weksler B, Romero IA, Hossain M, Rapp E, et al. Immortalized human brain endothelial cells and flow-based vascular modelling: A marriage of convenience for rational neurovascular studies. J Cereb Blood Flow Metab 2008; 28: 312-28.
49. Rubin, L.L., Porter, S., Horner, H.C., Yednick, T.A. Blood-brain barrier model. US5260210 (1993).
50. Shusta, E.V., Weidenfeller, C., Svedensen, C.N. Blood-brain barrier model. US20080044847 (2008).
51. Esser, P., Stigborg, F.T., Pedersen, K., Iskov, S. Culture insert carrier, culture insert and culture insert system. US20080194017 (2008).
52. Candela P, Gosselet F, Miller F, Blue-Scherrer V, Torpire G, Cecchelli R, et al. Physiological pathway for low-density lipoproteins across the blood-brain-barrier: Transcytosis through brain capillary endothelial cells in vitro. Endothelium 2008; 15: 254-64.
53. Hemmila JM, Drewes LR. Glucose transporter (GLUT1) expression by canine brain microvessel endothelial cells in culture: An immunocytochemical study. Adv Exp Med Biol 1993; 331: 13-8.
54. Nishizaki T, Kammesheidt A, Sumikawa K, Asada T, Okada Y. A sodium- and energy-dependent glucose transporter with similarities to SGLT1-2 is expressed in bovine cortical vessels. Neurosci Res 1995; 22: 13-22.
55. Tomi M, Kitade N, Hirose S, Yokota N, Akanuma S, Tachikawa M, et al. Cationic amino acid transporter 1-mediated L-arginine transport at the inner blood-retinal barrier. J Neurochem 2009; 111; 716-25.
56. Boado RK, Li JY, Zhang C, Pardridge WM. Selective expression of the large neutral amino acid transporter at the blood-brain barrier. Proc Natl Acad Sci USA 1999; 96: 12079-84.
57. Kageyama T, Nakamura M, Matsuo A, Yamasaki Y, Takakura Y Hashida M, et al. The 4F2hc/LAT1 complex transports L-DOPA across the blood-brain barrier. Brain Res 2000; 87: 115-21.
58. Lyck R, Ruderisch N, Moll AG, Steiner O, Cohen CD, Engelhardt B, et al. Culture-induced changes in blood-brain barrier transcriptome: Implications for amino-acid transporters in vivo. J Cereb Blood Flow Metab 2009; 29: 1491-502.
59. Tetsuka K, Takanaga H, Ohtsuki S, Hosova K, Terasaki T. The l-isomer-selective transport of aspartic acid is mediated by ASCT2 at the blood-brain barrier. J Neurochem 2003; 87; 891-901.
60. Scumpia PO, Kelly KM, Reeves WH, Stevens BR. Double-stranded RNA signals antiviral and inflammatory programs and dysfunctional glutamate transport in TLR3-expressing astrocytes. Glia 2005; 52: 153-62.
61. Kanq YS, Ohtsuki S, Takanaga H, Tomi M, Hosova K, Terasaki T. Regulation of taurine transport at the blood-brain barrier by tumor necrosis factor-alpha, taurine and hypertonicity. J Neuroschem 2002; 83: 1188-95.
62. Kitano T, Lizasa H, Terasaki T, Asahima T, Matsunaga N, Utoguchi N, et al. Polarized glucose transporters and mRNA expression properties in newly developed rat syncytiotrophoblast cell lines, TR-TBTs. J Cell Physiol 2002; 93: 208-18.
63. Cansey M. Uridine and cytidine in the brain: Their transport and utilization. Brain Res Rev 2006; 52: 389-97.
64. Kido Y, Tamai I, Okamoto M, Suzuki F, Tsuji A. Functional clarification of MCT1-mediated transport of monocarboxylic acids at the blood-brain barrier using in vitro cultured cells and in vivo BUI studies. Pharm Res 2000; 17: 55-62.
65. Yokel RA, Wilson M, Harris WR, Halestrap AP. Aluminum citrate uptake by immortalized brain endothelial cells: Implications for its blood-brain barrier transport. Brain Res 2002; 930: 101-10.
66. Sugiyama D, Usuhara H, Shitara Y, Abe T, Meier PJ, Sekine T, et al. Characterization of the efflux transport of 17 beta-estradiol-D-17beta-glucuronide from the brain across the blood-brain barrier. J Pharmacol Exp Ther 2001; 298: 316-22.
67. Sung JH, Yu KH, Park JS, Tsuruo T, Kim DD Shim CK, et al. Saturable distribution of tacrine into the striatal extracellular fluid of the rat: Evidence of involvement of multiple organic cation transporters in the transport. Drug Metb Dispos 2005; 33; 440-8.
68. Kang YS, Lee KE, Lee NY, Terasaki T. Donepezil, tacrine and alpha-phenyl-n-tert-butyl nitrone (PBN) inhibit choline transport by conditionally immortalized rat brain capillary endothelial cell lines (TR-BBB). Arch Pharm Res 2005; 28: 443-50.
69. Kido Y, Tamai I, Ohnari A, Sai Y, Kagami T, Nezu J, et al. Functional relevance of carnitine transporter OCTN2 to brain distribution of L-carnitine and acetyl-L-carnitine across the blood-brain barrier. J Neurochem 2001; 79: 959-9.
70. André P, Debray M, Schermann JM, Cisternino S. Clonidine transport at the mouse blood-brain barrier by a new H+ antiporter that interacts with addictive drugs. J Cereb Blood Flow Metab 2009; 29: 1293-304.
71. Visser CC, Stevanovic S, Heleen-Voorwinden L, Gaillard PJ, Gaillard PJ, Crommelin DJ, et al. Validation of the transferrin receptor for drug targeting to brain capillary endothelial cells in vitro. J Drug Target 2004; 12: 145-50.
72. Demeule M, Poirier J, Jodoin J, Bertrand Y, Desrosiers RR, Dagenais C, et al. High transcytosis of melanotransferrin (P97) across the blood-brain barrier. J Neurochem 2002; 83: 924-33.
73. Demeule M, Régina A, Jodoin J, Laplante A, Dagenais C, Berthelet F, et al. Drug transport to the brain: Key roles for the efflux pump P-glycoprotein in the blood-brain barrier. Vascul Pharmacol 2002; 38: 339-48.
74. Talukder MJ, Takeuchi T, Harada E. Receptor-mediated transport of lactoferrin into the cerebrospinal fluid via plasma in young calves. J Vet Med Sci 2003; 65: 957-64.
75. Deane R, Zlokovic BV. Role of the blood-brain barrier in the pathogenesis of Alzheimer's disease. Curr Alzheimer Res 2007; 4: 191-7.
76. Zlokovic BV. Cerebrovascular transport of Alzheimer's amyloid beta and apolipoproteins J and E: Possible anti-amyloidogenic role of the blood-brain barrier. Life Sci 1996; 59: 1483-97.
77. Kim DH, Lijima H, Goto K, Sakai J, Ishii H, Kim HJ, et al. Human apolipoprotein E receptor 2. A novel lipoprotein receptor of the low density lipoprotein receptor family predominantly expressed in brain. J Biol Chem 1996; 271: 8373-80.
78. D'Arcangelo G. Apoer 2: A reelin receptor to remember. Neuron 2005; 47: 471-3.
79. Mackic JB, Stins M, McComb JG, Calero M, Guiso J, Kim KS, et al. Human blood-brain barrier receptors for Alzheimer's amyloid-beta 1-40. Asymmetrical binding, endocytosis, and transcytosis at the apical side of brain microvascular endothelial cell monolayer. J Clin Invest 1998; 102: 734-43.
80. Deane R, Yan DS, Submamarvan RK, LaRue B, Jovanovic S, Hoqq E, et al. RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nat Med 2003; 9: 907-13.
81. Laron Z. Insulin and the brain. Arch Physiol Biochem 2009; 115: 112-6.
82. Jones AR, Shusta EV. Blood-brain barrier transport of therapeutics via receptor-mediation. Pharm Res 2007; 24: 1759-71.
83. Urayama A, Grubb JH, Sly WS, Banks WA. Developmentally regulated mannose 6-phosphate receptor-mediated transport of a lysosomal enzyme across the blood-brain barrier. Proc Natl Acad Sci USA 2004; 101:12658-63.
84. Boado RJ, Golden PL, Levin N, Pardridge WM. Up-regulation of blood-brain barrier short-form leptin receptor gene products in rats fed a high fat diet. J Neurochem 1998; 71: 1761-4.
85. Pan W, Kastin AJ. TNF alpha transport across the blood-brain barrier is abolished in receptor knockout mice. Exp Neurol 2002; 174: 193-200.
86. Wosik K, Biernacki K, Khouzam MP, Prat A. Death receptor expression and function at the human blood brain barrier. J Neurol Sci 2007; 259: 53-60.
87. Kurihara A, Deguchi Y, Pardridge WM. Epidermal growth factor radiopharmaceuticals: 111In chelation, conjugation to a blood-brain barrier delivery vector via a biotin-polyethylene linker, pharmacokinetics, and in vivo imaging of experimental brain tumors. Bioconjug Chem 1999; 10: 502-11.
88. Pan W, Kastin AJ. Entry of EGF into brain is rapid and saturable. Peptides 1999; 20: 1091-8.
89. Gaillard PJ, Visser CC, de Boer AG. Targeted delivery across the blood-brain barrier. Expert Opin Drug Deliv 2005; 2: 299-309.
90. Pan W, Cain C, Yu Y, Kastin AJ. Receptor-mediated transport of LIF across blood-spinal cord barrier is upregulated after spinal cord injury. J Neuroimmnunol 2006; 174; 119-25.
91. Rosenstein JM. Permeability of the blood-brain barrier to protein and [3H] GABA in intraparenchymal fetal CNS tissue grafts. Exp Neurol 1996; 142: 66-79.
92. Terasaki T, Hosoya K. The blood-brain barrier efflux transporters as a detoxifying system for the brain. Adv Drug Deliv Rev 1999; 36: 195-9.
93. Matsuo Y, Mihara S, Ninomiya M, Fujimoto M. Protective effect of endothelin type A receptor antagonist on brain edema and injury after transient middle cerebral artery occlusion in rats. Stroke 2001; 32: 2143-8.
94. Walsh RJ, Slaby FJ, Posner BI. A receptor-mediated mechanism for the transport of prolactin from blood to cerebrospinal fluid. Endocrinology 1987; 120: 1846-50.
95. Di Carlo R, Muccioli G, Papotti M, Bussolati G. Characterization of prolactin receptor in human brain and choroid plexus. Brain Res 1992; 570: 341-6.
96. Lindvall M, Edvinson L, Owman C. Histochemical, ultrastructural, and functional evidence for a neurogenic control of CSF production from the choroid plexus. Adv Neurol 1978; 20: 111-20.
97. Lobie PE, García-Aragón J, Lincoln DT, Barnard R, Wilcox JN, Waters MJ. Localization and ontogeny of growth hormone receptor gene expression in the central nervous system. Brain Res Dev Brain Res 1993; 74: 225-33.
98. Luder AS, Tanner SM, de la Chapelle A, Walter JH. Amnionless (AMN) mutations in Imerslund-Gräsbeck syndrome may be associated with disturbed Vitamin B (12) transport into the CNS. J Inherit Metab Dis 2008; [Epub ahead of print].
99. Saito A, Pietromonaco S, Loo AK, Farquhar MG. Complete cloning and sequencing of rat gp330/megalin, a distinctive member of the low density lipoprotein receptor gene family. Proc Natl Aacad Sci USA 1994; 91: 9725-9.
100. Chowdhary BP, Lundgren S, Johanson M, Hjälm G, Akertsröm G, Gustavsson I, et al. In situ hybridization mapping of a 500-kDa calcium-sensing protein gene (LRP2) to human chromosome region 2q31-->q32.1 and porcine chromosome region 15q22>q24. Cytogenet Cell Genet 1995; 71: 120-3.
101. Herz J, Bock HH. Lipoprotein receptors in the nervous system. Annu Rev Biochem 2002; 71: 405-34.
102. Christensen EI, Birn H. Megalin and cubilin: Multifunctional endocytic receptors. Nat Rev Mol Cell Biol 2002; 3: 256-66.
103. Kounnas MZ, Haudenschild CC, Strickland DK, Argraves WS. Immunological localization of glycoprotein 330, low density lipoprotein receptor related protein and 39 kDa receptor associated protein in embryonic mouse tissues. In Vivo 1994; 8: 343-51.
104. Willnow TE, Hilpert J, Armstrong SA, Rohlmann A, Hammer RE, Burns DK, et al. Defective forebrain development in mice lacking gp330/megalin. Proc Natl Acad Sci USA 1996; 93: 8460-4.
105. Chun JT, Wang L, Pasinetti GM, Finch CE, Zlokovic BV. Glycoprotein 330/megalin (LRP-2) has low prevalence as mRNA and protein in brain microvessels and choroid plexus. Exp Neurol 1999; 157: 194-201.
106. Nykjaer A, Dragun D, Walther D, Vorum H, Jacobsen C, Herz J, et al. An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) Vitamin D3. Cell 1999; 19: 507-15.
107. Christensen EI, Moskaug JO, Vorum H, Jacobsen C, Gundersen TE, Nykjaer A, et al. Evidence for an essential role of megalin in transepithelial transport of retinol. J Am Soc Nephrol 1999; 10: 685-95.
108. Liu W, Yu WR, Carling T, Juhlin C, Rastad J, Ridefelt P, et al. Regulation of gp330/megalin expression by Vitamins A and D. Eur J Clin Invest 1998; 28: 100-7.
109. Moestrup SK, Schousboe I, Jacobsen C, Leheste JR, Christensen EI, Willnow TE. beta2-glycoprotein-I (apolipoprotein H) and beta2-glycoprotein-I-phospholipid complex harbour a recognition site for the endocytic receptor megalin. J Clin Invest 1998; 102: 902-9.
110. Duqué-Pujol S, Rousset X, Château D, Pastier D, Klein C, Demeurie J, et al. Apolipoprotein A-II is catabolized in the kidney as a function of its plasma concentration. J Lipd Res 2007; 48: 2151-61.
111. Faber K, Hvidberg V, Moestrup SK, Dahlbäck B, Nielsen LB. Megalin is a receptor for apolipoprotein M, and kidney-specific megalin-deficiency confers urinary excretion of apolipoprotein M. Mol Endocrinol 2006; 20: 212-8.
112. Hilpert J, Nykjaer A, Jacobsen C, Wallukat G, Nielsen R, Moestrup SK, et al. Megalin antagonizes activation of the parathyroid hormone receptor. J Biol Chem 1999; 274: 5620-5.
113. Sousa MM, Norden AG, Jacobsen C, Willnow TE, Christensen EI, Thakker RV, et al. Evidence for the role of megalin in renal uptake of transthyretin. J Biol Chem 2000; 275: 38176-81.
114. Marino M, Zheng G, Chiovato L, Pinchera A, Brown D, Andrews D, et al. Role of megalin (gp330) in transcytosis of thyroglobulin by thyroid cells. A novel function in the control of thyroid hormone release. J Biol Chem 2000; 275: 7125-37.
115. Orlando RA, Rader K, Authier F, Yamazaki H, Posner BI, Bergeron JJ, et al. Megalin is an endocytic receptor for insulin. J Am Soc Nephrol 1998; 9: 1759-66.
116. Torres-Aleman, I., Carro, E., Trejo, J.L., Spuch, C., Bohl, D., Heard, J.M. Animal model of neurodegenerative diseases, the procedure for producing the model and applications thereof. US20080038227 (2008).
117. Torres-Aleman, I., Carro, E., Bohl, D., Heard, J.M. Non human animal Alzheimer's disease model and uses thereof. US20070266450 (2007).
118. Wispelwey B, Lesse AJ, Hansen EJ, Scheld WM. Haemophilus influenzae lipopolysaccharide-induced blood brain barrier permeability during experimental meningitis in the rat. J Clin Invest 1988; 82: 1339-46.
119. Mazza M, Ucheqbu IF, Scätzlein AG. Cancer and the blood-brain barrier: 'Trojan horses' for courses? Br J Pharmacol 2008; 155: 149-51.
120. Jiao Y, Liu W. Low-density lipoprotein receptor-related protein 1 is an essential receptor for trichosanthin in 2 choriocarcinoma cell lines. Biochem Biophys Res Commun 2009; 391(4):1579-84.
121. Hultman K, Björklund U, Hansson E, Jern C. Potentiating effect of endothelial cells on astrocytic plasminogen activator inhibitor type-1 gene expression in an in vitro model of the blood-brain barrier. Neuroscience 2010; 166(2): 408-15.
122. Goti D, Balazs Z, Panzenboeck U, Hrzenjak A, Reicher H, Wagner E, et al. Effects of lipoprotein lipase on uptake and transcytosis of low density lipoprotein (LDL) and LDL-associated alpha-tocopherol in a porcine in vitro blood-brain barrier model. J Biol Chem 2002; 277: 28537-44.
123. Bento-Abreu A, Velasco A, Polo-Hernández E, Lillo C, Kozyraki R, Tabernero A, et al. Albumin endocytosis via megalin in astrocytes is caveola- and Dab-1 dependent and is required for the synthesis of the neurotrophic factor oleic acid. J Neurochem 2009; 111: 49-60.
124. Croy JE, Shin WD, Knauer MF, Komives EA. All three LDL receptor homology regions of the LDL receptor-related protein bind multiple ligands. Biochemistry 2003; 42: 13049-57.
125. Vrethem M, Henrjksson A, Malm C, Olsson T, Ernerudh J. Ig-secreting cells pass the blood-brain barrier: Studies on kappa and lambda light chain secreting cells in plasma cell dyscrasia. J Neuroimmunol 1992; 41: 189-94.
126. Siato A, Lino N, takeda T, Geivo F. Role of megalin, a proximal tubular endocytic receptor, in calcium and phosphate homeostasis. Ther Apher Dial 2007; 11: 23-6.
127. Klassen RB, Crenshaw K, Kozyraki R, Verroust PJ, Tjo L, Atrian S, et al. Megalin mediates renal uptake of heavy metal metallothionein complexes. Am J Physiol Renal Physiol 2004; 287: 393-403.
128. Moestrup SK, Birn H, Fisher PB, Petersen CM, Verroust PJ, Sim RB, et al. Megalin-mediated endocytosis of transcobalamin- Vitamin-B12 complexes suggests a role of the receptor in Vitamin B12 homeostasis. Proc Natl Acad Sci USA 1996; 93: 8612-7.
129. Chlon TM, Taffany DA, Welsh J, Rowling MJ. Retinoids modulate expression of the endocytic partners megalin, cubilin, and disabled- 2 and uptake of Vitamin D-binding protein in human mammary cells. J Nutr 2008; 138: 1323-8.
130. Raila J, Willnow TE, Schweigert FJ. Megalin-mediated reuptake of retinol in the kidneys of mice is essential for Vitamin A homeostasis. J Nutr 2005; 135: 2512-6.
131. Johanson CE, Klinge PM, Soltman S, Flaherty S, Messier A, Duncan JA, et al. Enhanced expression of the LRP-1 transporter at the blood-CSF interface in chronic hydrocephalus. Cerebrospinal Fluis Res 2007; 4: S45.
132. Zlokovic BV, Martel CL, Matsubara E, McComb JG, Zheng G, McCluskey RT, et al. Glycoprotein 330/megalin: Probable role in receptor-mediated transport of apolipoprotein J alone and in a complex with Alzheimer disease amyloid beta at the blood-brain and blood-cerebrospinal fluid barriers. Proc Natl Acad Sci USA 1996; 93: 4229-34.
133. Hammad SM, Ranganathan S, Loukinova A, Twal WO, Argraves WS. Interaction of apolipoprotein J-amyloid beta-peptide complex with low density lipoprotein receptor-related protein-2/megalin. A mechanism to prevent pathological accumulation of amyloid beta-peptide. J Biol Chem 1997; 272: 18644-9.
134. Müller D, Nykjaer A, Willnow TE. From holoprosencephaly to osteopathology: Role of multifunctional endocytic receptors in absorptive epithelia. Ann Med 2003; 35: 290-9.
135. Drake CJ, Fleming PA, Larue AC, Barth JL, Chintalapudi MR, Argraves WS. Differential distribution of cubilin and megalin expression in the mouse embryo. Anat Rec A Discov Mol Cell Evol Biol 2004; 277: 163-70.
136. McCarthy RA, Barth JL, Chintalapudi MR, Knaak C, Argraves WS. Megalin functions as an endocytic sonic hedgehog receptor. J Biol Chem 2002; 277: 25660-7.
137. Gotthardt M, Trommsdorff M, Nevitt MF, Shelton J, Richardson JA, Stockinger W, et al. Interactions of the low density lipoprotein receptor gene family with cytosolic adaptor and scaffold proteins suggest diverse biological functions in cellular communication and signal transduction. J Biol Chem 2000; 275: 25616-24.
138. Larsson M, Hjalm G, Sakwe AM, Engstrom A, Hoglund AS, Larsson E, et al. Selective interaction of megalin with postsynaptic density-95 (PSD-95)-like membrane-associated guanylate kinase (MAGUK) proteins. Biochem J 2003; 373: 381-91.
139. Oleinikov AV, Zhao J, Makker SP. Cytosolic adaptor protein Dab2 is an intracellular ligand of endocytic receptor gp600/megalin. Biochem J 2000; 347: 613-21.
140. Nagai M, Meerloo T, Takeda T, Farquhar M. The adaptor protein ARH escorts megalin to and through endosomes. Mol Biol Cell 2003; 14: 4984-96.
141. Radzimanowski J, Ravaud S, Schlesinger S, Koch J, Bevreuther K, Sinning I, et al. Crystal structure of the human Fe65-PTB1 domain. J Biol Chem 2008; 283: 23113-20.
142. Biemedderfer D. Regulated intramembrane proteolysis of megalin: linking urinary protein and gene regulation in proximal tubule. Kidney Int 2006; 69: 1717-21.
143. Ishida T, Hatae T, Nishi N, Araki N. Soluble megalin is accumulated in the lumen of the rat endolymphatic sac. Cell Struct Funct 2006; 31: 77-85.
144. Sagare A, Deane R, Bell RD, Johnson B, Hamm K, Pendu R, et al. Clearance of amyloid-beta by circulating lipoprotein receptors. Nat Med 2007; 13: 1029-31.
145. Farquhar MG, Kerjaschki D, Lundstrom M, Orlando RA. Gp330 and RAP: The Heymann nephritis antigenic complex. Ann N Y Acad Sci 1994;/737:/96-113.
146. 2+ sensing protein. J Hystochem Cytochem 1997; 45: 383-92.
147. Lisi S, Pinchera A, McCluskey RT, Willnow TE, Refetoff S, Marcocci C, et al. Preferential megalin-mediated transcytosis of low-hormonogenic thyroglobulin: A control mechanism for thyroid hormone release. Proc Natl Acad Sci USA 2003; 100: 14858-63.
148. Rüstow B, Haupt R, Stevens PA, Kunze D. Type II pneumocytes secrete Vitamin E together with surfactant lipids. Am J Physiol 1993; 265: 133-8.
149. Birn H, Verroust PJ, Nexo E, Hager H, Jacobsen C, Christensen EI, et al. Characterization of an epithelial approximately 460-kDa protein that facilitates endocytosis of intrinsic factor-Vitamin B12 and binds receptor-associated protein. J Biol Chem 1997; 272: 26497-504.
150. Moestrup SK, Kozyraki R, Kristiansen M, Kaysen JH, Rasmussen HH, Brault D, et al. The intrinsic factor-Vitamin B12 receptor and target of teratogenic antibodies is a megalin-binding peripheral membrane protein with homology to developmental proteins. J Biol Chem 1998; 273: 5323-42.
151. Tauris J, Christensen EI, Nykjaer A, Jacobsen C, Petersen CM, Ovesen T. Cubilin and megalin co-localize in the neonatal inner ear. Audiol Neurootol 2009; 14: 267-78.
152. Fleming CE, Mar FM, Franquinho F, Saraiva MJ, Sousa MM. Transthyretin internalization by sensory neurons is megalin mediated and necessary for its neuritogenic activity. J Neurosci 2009; 29: 3220-32.
153. Carro E, Trejo JL, Gomez-Isla T, LeRoith D, Torres-Aleman I. Serum insulin-like growth factor I regulates brain amyloid-beta levels. Nat Med 2002; 8: 1390-7.
154. Carro EM. Therapeutic approaches of leptin in Alzheimer's disease. Recent Pat CNS Drug Discov 2009; 4: 200-8.
155. Vargas T, Bullido MJ, Martinez-Garcia A, Antequera D, Clarimon J, Rosich-Estrago M, et al. A megalin polymorphism associated with promoter activity and Alzheimer's disease risk. Am J Med Genet B Neuropsyquiatr Genet 2010; 153B(4): 895-902.
156. Holt SK, Karyadi DM, Kwon EM, Stanford JL, Nelson PS, Ostrander EA. Association of megalin genetic polymorphisms with prostate cancer risk and prognosis. Clin Cancer Res 2008; 15: 3823-31.
157. Mij A, Nakajima T, Fujita Y, Iino Y, Kamimura K, Bujo H, et al. Genetic association of low-density lipoprotein receptor-related protein 2 (LRP2) with plasma lipid levels. J Atheroescler Thromb 2007; 14: 310-6.
158. Junq FF, Bachinsky DR, Tanq SS, Zheng G, Diamant D, Haveran L, et al. Immortalized rat proximal tubule cells produce membrane bound and soluble megalin. Kidney Int 1998: 53: 358-66.
159. Vargas T, Ugalde C, Spuch C, Antequera D, Moran MJ, Martin MA, et al. Abeta accumulation in choroid plexus is associated with mitochondrial-induced apoptosis. Neurobiol Aging 2008; [Epub ahead of print].
160. Zlokovic, B., Deane, R. Soluble low density lipoprotein receptor related protein binds directly to Alzheimer's amyloid beta peptide. US20070054318 (2007).
161. Relkin NR, Szabo P, Adamiak B, Bugut T, Monthe C, Lent RW, et al. 18-Month study of intravenous immunoglobulin for treatment of mild Alzheimer disease. Neurobiol Aging 2009; 30: 1728-36.
162. O'Nuakkain B, Acero L, Williams AD, Koeppen HP, Weber A, Schwarz HP, et al. Human plasma contains cross-reactive Abeta conformer-specific IgG antibodies. Biochemistry 2008; 47: 12254-6.
163. Sannerud R, Annaert W. Trafficking, a key player in regulated intramembrane proteolysis. Semin Cell Dev Biol 2009; 20: 183-90.
164. Edwards DR, Handsley MM, Pennington CJ. The ADAM metalloproteinases. Mol Aspects Med 2008; 29: 258-89.
165. Vassar R, Kovacs DM, Yan R, Wong PC. The beta-secretase enzyme BACE in health and Alzheimer's disease: Regulation, cell biology, function, and therapeutic potential. J Neurosci 2009; 29: 12787-94.
166. Bronfman FC. Metalloproteases and gamma-secretase: New membrane partners regulating p75 neurotrophin receptor signaling? J Neurochem 2007; 103: 91-100.
167. Biemesderfer D. Regulated intramembrane proteolysis of megalin: Linking urinary protein and gene regulation in proximal tubule? Kidney Int 2006; 69: 1717-21.
168. Li Y, Cong R, Biemesderfer D. The COOH terminus of megalin regulates gene expression in opossum kidney proximal tubule cells. Am J Physiol Cell Physiol 2008; 295: 529-37.
169. Mochly-Rosen, D.D., Qi, X., Inagaki, K. Methods for maintaining blood brain barrier integrity in hypertensive subjects using a delta-PKC inhibitor. US20090062208 (2009).
170. Yoon IS, Chen E, Busse T, Repetto E, Lakshmana MK, Koo EH, et al. Low-density lipoprotein receptor-related protein promotes amyloid precursor protein trafficking to lipid rafts in the endocytic pathway. FASEB J 2007; 21: 2742-52.
171. Trommsdorff M, Borq JP, Margolis B, Herz J. Interaction of cytosolic adaptor proteins with neuronal apolipoprotein E receptors and the amyloid precursor protein. J Biol Chem 1998; 273: 33556-60.
172. Morris SM, Tallquist MD, Rock CO, Cooper JA. Dual roles for the Dab2 adaptor protein in embryonic development and kidney transport. EMBO J 2002; 21: 1555-64.
173. Esmond, R.W., Wands, J.R. Method for treating or preventing Alzheimer's disease. US20090280192 (2009).
174. Zlokovic, B., Wu, Z., Deane, R. Role of GAX in Alzheimer neurovascular dysfunction. US20090181911 (2009).
175. Grasso, P., Lee, D.W., Leinung, M.C. Leptin related peptides. US7208572 (2007).
176. Pan W, Kastin AJ, Zankel TC, van Kerkhof P, Terasaki T, Bu G. Efficient transfer of receptor-associated protein (RAP) across the blood-brain barrier. J Cell Sci 2004; 117: 5071-8.
177. Starr, C.M., Zankel, T.C. Compositions comprising receptor associated protein (RAP) variants specific for LRP2 and uses thereof. US20090269346 (2009).
178. Kanekiyo T, Bu G. Receptor-associated protein interacts with amyloid beta peptide and promotes its cellular uptake. J Biol Chem 2009; 284: 33352-9.
179. Yuseff MI, Farfan P, Bu G, Marzolo MP. A cytoplasmic PPPSP motif determines megalin's phosphorylation and regulates receptor's recycling and surface expression. Traffic 2007; 8: 1215-30.