Polymeric alkylpyridinium salts permit intracellular delivery of human Tau in rat hippocampal neurons: Requirement of Tau phosphorylation for functional deficits

Cellular and Molecular Life Sciences

Volumn 72, Issue 23, 2015, Pages 4613-4632

  Koss, Dave J ^a   Robinson, Lianne ^a,d   Mietelska Porowska, Anna ^b   Gasiorowska, Anna ^b,e   Sepčić, Kristina ^c   Turk, Tom ^c   Jaspars, Marcel ^a   Niewiadomska, Grazyna ^b   Scott, Roderick H ^a   Platt, Bettina ^a   Riedel, Gernot ^a  

^a UNIVERSITY OF ABERDEEN   (United Kingdom)

^b NENCKI INSTITUTE OF EXPERIMENTAL BIOLOGY   (Poland)

^c UNIVERSITY OF LJUBLJANA   (Slovenia)

^d UNIVERSITY OF DUNDEE   (United Kingdom)

^e MOSSAKOWSKI MEDICAL RESEARCH CENTRE   (Poland)

Author keywords

Alzheimer's disease; Calcium; Frontotemporal dementia; LTP; Phospho Tau; Poly APS; Tau; Tauopathies

Indexed keywords

CALCIUM ION; GLUTAMIC ACID; HUMAN TAU PROTEIN; INORGANIC SALT; OKADAIC ACID; POLYMERIC 1,3 ALKYLPYRIDINIUM SALT; POTASSIUM CHLORIDE; TAU PROTEIN; UNCLASSIFIED DRUG; POLY-APS; POLYMER; PYRIDINIUM DERIVATIVE; RECOMBINANT PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIOACCUMULATION; CALCIUM HOMEOSTASIS; CALCIUM SIGNALING; COGNITIVE DEFECT; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; DISEASE ASSOCIATION; DORSAL HIPPOCAMPUS; ELECTROPHYSIOLOGY PARAMETERS; EMBRYO; ENZYME ACTIVITY; ENZYME INHIBITION; HIPPOCAMPAL CA1 REGION; HIPPOCAMPAL NEURONAL CULTURE; HISTOPATHOLOGY; IN VITRO STUDY; IN VIVO STUDY; INCUBATION TIME; INPUT RESISTANCE; INTRACELLULAR SIGNALING; LEARNING DISORDER; MALE; MEMBRANE POTENTIAL; MEMORY DISORDER; MOLECULAR DYNAMICS; NERVE CELL PLASTICITY; NEUROPATHOLOGY; NONHUMAN; PROTEIN PHOSPHORYLATION; PROTEIN TRANSPORT; PYRAMIDAL NERVE CELL; RAT; RECALL; RESTING STATE MEMBRANE POTENTIAL; SPATIAL LEARNING; SYMPTOM; TAUOPATHY; ANIMAL; ANIMAL BEHAVIOR; CELL CULTURE; CYTOLOGY; DISEASE MODEL; DRUG EFFECTS; ELECTROPHYSIOLOGY; HIPPOCAMPUS; HUMAN; LEARNING DISORDERS; METABOLISM; NERVE CELL; PHOSPHORYLATION; PHYSIOLOGY; PROCEDURES; SPRAGUE DAWLEY RAT;

ANIMALS; BEHAVIOR, ANIMAL; CALCIUM SIGNALING; CELLS, CULTURED; DISEASE MODELS, ANIMAL; ELECTROPHYSIOLOGY; HIPPOCAMPUS; HUMANS; LEARNING DISORDERS; MALE; NEURONAL PLASTICITY; NEURONS; PHOSPHORYLATION; POLYMERS; PYRIDINIUM COMPOUNDS; RATS, SPRAGUE-DAWLEY; RECOMBINANT PROTEINS; TAU PROTEINS; TAUOPATHIES;

EID: 84946484207     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-015-1949-4     Document Type: Article

References (125)

1. Pryer NK, Walker RA, Skeen VP, Bourns BD, Soboeiro MF, Salmon ED (1992) Brain microtubule-associated proteins modulate microtubule dynamic instability in vitro Real-time observations using video microscopy. J cell Sci 103(4):965-976
2. Niewiadomska G, Baksalerska-pazera M, Lenarcik I (1996) Riedel G (2006) Compartmental protein expression of Tau, GSK-3beta and TrkA in cholinergic neurons of aged rats. J Neural Transm Vienna Austria 113(11):1733-1746
3. Spillantini MG, Goedert M (2000) Tau mutations in familial frontotemporal dementia. Brain J Neurol 123(5):857-859
4. Rapoport M, Dawson HN, Binder LI, Vitek MP, Ferreira A (2002) Tau is essential to beta -amyloid-induced neurotoxicity. Proc Natl Acad Sci USA 99(9):6364-6369
5. Goedert M, Wischik CM, Crowther RA, Walker JE, Klug A (1988) Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein Tau. Proc Natl Acad Sci USA 85(11):4051-4055
6. Crowther RA (1991) Straight and paired helical filaments in Alzheimer disease have a common structural unit. Proc Natl Acad Sci USA 88(6):2288-2292
7. Giannakopoulos P, Herrmann FR, Bussiere T, Bouras C, Kovari E, Perl DP, Morrison JH, Gold G, Hof PR (2003) Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease. Neurology 60(9):1495-1500
8. Guillozet AL, Weintraub S, Mash DC, Mesulam MM (2003) Neurofibrillary tangles, amyloid, and memory in aging and mild cognitive impairment. Arch Neurol 60(5):729-736
9. Morishima-kawashima M, Hasegawa M, Takio K, Suzuki M, Yoshida H, Watanabe A, Titani K, Ihara Y (1995) Hyperphosphorylation of Tau in PHF. Neurobiol Aging 16(3):365-371 (discussion 371-80)
10. Wang JZ, Grundke-Iqbal I, Iqbal K (2007) Kinases and phosphatases and Tau sites involved in Alzheimer neurofibrillary degeneration. The European journal of neuroscience 25(1):59-68
11. Williamson R, Scales T, Clark BR, Gibb G, Reynolds CH, Kellie S, Bird IN, Varndell IM, Sheppard PW, Everall I, Anderton BH (2002) Rapid tyrosine phosphorylation of neuronal proteins including Tau and focal adhesion kinase in response to amyloid-beta peptide exposure: involvement of Src family protein kinases. J Neurosci Off J Soc Neurosci 22(1):10-20
12. Lee G, Thangavel R, Sharma VM, Litersky JM, Bhaskar K, Fang SM, Do LH, Andreadis A, van Hoesen G, Ksiezak-Reding H (2004) Phosphorylation of Tau by fyn: implications for Alzheimer's disease. J Neurosci Off J Soc Neurosci 24(9):2304-2312
13. Derkinderen P, Scales TM, Hanger DP, Leung KY, Byers HL, Ward MA, Lenz C, Price C, Bird IN, Perera T, Kellie S, Williamson R, Noble W, van Etten RA, Leroy K, Brion JP, Reynolds CH, Anderton BH (2005) Tyrosine 394 is phosphorylated in Alzheimer's paired helical filament Tau and in fetal Tau with c-Abl as the candidate tyrosine kinase. J Neurosci Off J Soc Neurosci 25(28):6584-6593
14. Mietelska-Porowska A, Wasik U, Goras M, Filipek A, Niewiadomska G (2014) Tau protein modifications and interactions: their role in function and dysfunction. Int J Mol Sci 15(3):4671-4713
15. Cruz JC, Tseng HC, Goldman JA, Shih H, Tsai LH (2003) Aberrant Cdk5 activation by p25 triggers pathological events leading to neurodegeneration and neurofibrillary tangles. Neuron 40(3):471-483
16. Braak H, Braak E (1996) Evolution of the neuropathology of Alzheimer's disease. Acta Neurol Scand Suppl 165:3-12
17. Lauckner J, Frey P, Geula C (2003) Comparative distribution of Tau phosphorylated at Ser262 in pre-tangles and tangles. Neurobiol Aging 24(6):767-776
18. Biernat J, Mandelkow EM (1999) The development of cell processes induced by Tau protein requires phosphorylation of serine 262 and 356 in the repeat domain and is inhibited by phosphorylation in the proline-rich domains. Mol Biol Cell 10(3):727-740
19. Berger Z, Roder H, Hanna A, Carlson A, Rangachari V, Yue M, Wszolek Z, Ashe K, Knight J, Dickson D, Andorfer C, Rosenberry TL, Lewis J, Hutton M, Janus C (2007) Accumulation of pathological Tau species and memory loss in a conditional model of tauopathy. J Neurosci Off J Soc Neurosci 27(14):3650-3662
20. Flunkert S, Hierzer M, Loffler T, Rabl R, Neddens J, Duller S, Schofield EL, Ward MA, Posch M, Jungwirth H, Windisch M, Hutter-Paier B (2013) Elevated levels of soluble total and hyperphosphorylated Tau result in early behavioral deficits and distinct changes in brain pathology in a new Tau transgenic mouse model. Neuro-degenerative diseases 11(4):194-205
21. Fox LM, William CM, Adamowicz DH, Pitstick R, Carlson GA, Spires-Jones TL, Hyman BT (2011) Soluble Tau species, not neurofibrillary aggregates, disrupt neural system integration in a Tau transgenic model. J Neuropathol Exp Neurol 70(7):588-595
22. Santacruz K, Lewis J, Spires T, Paulson J, Kotilinek L, Ingelsson M, Guimaraes A, Deture M, Ramsden M, McGowan E, Forster C, Yue M, Orne J, Janus C, Mariash A, Kuskowski M, Hyman B, Hutton M, Ashe KH (2005) Tau suppression in a neurodegenerative mouse model improves memory function. Sci (New York, NY) 309(5733):476-481
23. Sydow A, Mandelkow EM (2010) 'Prion-like' propagation of mouse and human Tau aggregates in an inducible mouse model of tauopathy. Neuro-degenerative Dis 7(1-3):28-31
24. Planel E, Miyasaka T, Launey T, Chui DH, Tanemura K, Sato S, Murayama O, Ishiguro K, Tatebayashi Y, Takashima A (2004) Alterations in glucose metabolism induce hypothermia leading to Tau hyperphosphorylation through differential inhibition of kinase and phosphatase activities: implications for Alzheimer's disease. J Neurosci Off J Soc Neurosci 24(10):2401-2411
25. Zhu D, Kosik KS, Meigs TE, Yanamadala V, Denker BM (2004) Galpha12 directly interacts with PP2A: evidence FOR Galpha12-stimulated PP2A phosphatase activity and dephosphorylation of microtubule-associated protein Tau. J Biol Chem 279(53):54983-54986
26. Sontag E, Nunbhakdi-Craig V, Bloom GS, Mumby MC (1995) A novel pool of protein phosphatase 2A is associated with microtubules and is regulated during the cell cycle. J Cell Biol 128(6):1131-1144
27. Sontag E, Nunbhakdi-Craig V, Lee G, Bloom GS, Mumby MC (1996) Regulation of the phosphorylation state and microtubule-binding activity of Tau by protein phosphatase 2A. Neuron 17(6):1201-1207
28. Liao H, Li Y, Brautigan DL, Gundersen GG (1998) Protein phosphatase 1 is targeted to microtubules by the microtubule-associated protein Tau. J Biol Chem 273(34):21901-21908
29. Gong CX, Liu F, Wu G, Rossie S, Wegiel J, Li L, Grundke-Iqbal I, Iqbal K (2004) Dephosphorylation of microtubule-associated protein Tau by protein phosphatase 5. J Neurochem 88(2):298-310
30. Liu F, Grundke-Iqbal I, Iqbal K, Gong CX (2005) Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of Tau phosphorylation. Eur J Neurosci 22(8):1942-1950
31. Sontag E, Hladik C, Montgomery L, Luangpirom A, Mudrak I, Ogris E, White CL III (2004) Downregulation of protein phosphatase 2A carboxyl methylation and methyltransferase may contribute to Alzheimer disease pathogenesis. J Neuropathol Exp Neurol 63(10):1080-1091
32. Sontag E, Luangpirom A, Hladik C, Mudrak I, Ogris E, Speciale S, White CL III (2004) Altered expression levels of the protein phosphatase 2A ABalphaC enzyme are associated with Alzheimer disease pathology. J Neuropathol Exp Neurol 63(4):287-301
33. Tanimukai H, Grundke-Iqbal I, Iqbal K (2005) Up-regulation of inhibitors of protein phosphatase-2A in Alzheimer's disease. Am J Pathol 166(6):1761-1771
34. Goedert M, Satumtira S, Jakes R, Smith MJ, Kamibayashi C, White CL III, Sontag E (2000) Reduced binding of protein phosphatase 2A to Tau protein with frontotemporal dementia and parkinsonism linked to chromosome 17 mutations. J Neurochem 75(5):2155-2162
35. Li R, Xu DE, Ma T (2015) Lovastatin suppresses the aberrant tau phosphorylation from FTDP-17 mutation and okadaic acid-induction in rat primary neurons. Neuroscience 294:14-20
36. Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82(4):239-259
37. Melis V, Zabke C, Stamer K, Magbagbeolu M, Schwab K, Marschall P, Veh RW, Bachmann S, Deiana S, Moreau P, Davidson K, Harrington KA, Rickard JE, Horsley D, Garman R, Mazurkiewicz M, Niewiadomska G, Wischik CM, Harrington CR, Riedel G, Theuring F (2014) Different pathways of molecular pathophysiology underlie cognitive and motor tauopathy phenotypes in transgenic models for Alzheimer's disease and frontotemporal lobar degeneration. Cell Mol Life Sci CMLS. doi: 10.1007/s00018-014-1804-z
38. Jucker M, Walker LC (2011) Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders. Ann Neurol 70(4):532-540
39. Stohr J, Watts JC, Mensinger ZL, Oehler A, Grillo SK, Dearmond SJ, Prusiner SB, Giles K (2012) Purified and synthetic Alzheimer's amyloid beta (Abeta) prions. Proc Natl Acad Sci USA 109(27):11025-11030
40. Clavaguera F, Bolmont T, Crowther RA, Abramowski D, Frank S, Probst A, Fraser G, Stalder AK, Beibel M, Staufenbiel M, Jucker M, Goedert M, Tolnay M (2009) Transmission and spreading of tauopathy in transgenic mouse brain. Nat Cell Biol 11(7):909-913
41. Yoshiyama Y, Higuchi M, Zhang B, Huang SM, Iwata N, Saido TC, Maeda J, Suhara T, Trojanowski JQ, Lee VM (2007) Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53(3):337-351
42. Peeraer E, Bottelbergs A, Van Kolen K, Stancu IC, Vasconcelos B, Mahieu M, Duytschaever H, Ver Donck L, Torremans A, Sluydts E, Van Acker N, Kemp JA, Mercken M, Brunden KR, Trojanowski JQ, Dewachter I, Lee VM, Moechars D (2015) Intracerebral injection of preformed synthetic Tau fibrils initiates widespread tauopathy and neuronal loss in the brains of Tau transgenic mice. Neurobiol Dis 73:83-95
43. Dujardin S, Lecolle K, Caillierez R, Begard S, Zommer N, Lachaud C, Carrier S, Dufour N, Auregan G, Winderickx J, Hantraye P, Deglon N, Colin M, Buee L (2014) Neuron-to-neuron wild-type Tau protein transfer through a trans-synaptic mechanism: relevance to sporadic tauopathies. Acta Neuropathol Commun 2:14
44. Do Carmo S, Cuello AC (2013) Modeling Alzheimer's disease in transgenic rats. Mol Neurodegener 8:37
45. Lin JH (1995) Species similarities and differences in pharmacokinetics. Drug metabolism and disposition: the biological fate of chemicals 23(10):1008-1021
46. Jacob HJ, Kwitek AE (2002) Rat genetics: attaching physiology and pharmacology to the genome. Nat Rev Genet 3(1):33-42
47. McMillan P, Korvatska E, Poorkaj P, Evstafjeva Z, Robinson L, Greenup L, Leverenz J, Schellenberg GD, D'Souza I (2008) Tau isoform regulation is region- and cell-specific in mouse brain. J Comp Neurol 511(6):788-803
48. Hanes J, Zilka N, Bartkova M, Caletkova M, Dobrota D, Novak M (2009) Rat Tau proteome consists of six Tau isoforms: implication for animal models of human tauopathies. J Neurochem 108(5):1167-1176
49. Buee L, Bussiere T, Buee-Scherrer V, Delacourte A, Hof PR (2000) Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Brain Res Rev 33(1):95-130
50. Braak E, Braak H (1997) Alzheimer's disease: transiently developing dendritic changes in pyramidal cells of sector CA1 of the Ammon's horn. Acta Neuropathol 93(4):323-325
51. Cehlar O, Skrabana R, Kovac A, Kovacech B, Novak M (2012) Crystallization and preliminary X-ray diffraction analysis of Tau protein microtubule-binding motifs in complex with Tau5 and DC25 antibody Fab fragments. Acta Crystallogr Sect F Struct Biol Cryst Commun 68(10):1181-1185
52. Sepcic K, Batista U, Vacelet J, Macek P, Turk T (1997) Biological activities of aqueous extracts from marine sponges and cytotoxic effects of 3-alkylpyridinium polymers from Reniera sarai Comparative biochemistry and physiologyPart C. Pharmacol Toxicol Endocrinol 117(1):47-53
53. McClelland D, Evans RM, Abidin I, Sharma S, Choudhry FZ, Jaspars M, Sepcic K, Scott RH (2003) Irreversible and reversible pore formation by polymeric alkylpyridinium salts (poly-APS) from the sponge Reniera sarai. Br J Pharmacol 139(8):1399-1408
54. Tucker SJ, McClelland D, Jaspars M, Sepcic K, Macewan DJ, Scott RH (2003) The influence of alkyl pyridinium sponge toxins on membrane properties, cytotoxicity, transfection and protein expression in mammalian cells. Biochim Biophys Acta 1614(2):171-181
55. Koss DJ, Hindley KP, David KC, Mancini I, Guella G, Sepcic K, Turk T, Rebolj K, Riedel G, Platt B, Scott RH (2007) A comparative study of the actions of alkylpyridinium salts from a marine sponge and related synthetic compounds in rat cultured hippocampal neurones. BMC Pharmacol 7:1
56. Malovrh P, Sepcic K, Turk T, Macek P (1999) Characterization of hemolytic activity of 3-alkylpyridinium polymers from the marine sponge Reniera sarai Comparative biochemistry and physiologyPart C. Pharmacol Toxicol Endocrinol 124(2):221-226
57. Schmitz FJ, Hollenbeak KH, Campbell DC (1978) Marine natural products: halitoxin, toxic complex of several marine sponges of the genus Haliclona. J Org Chem 43:3916-3922
58. Berlinck RG, Ogawa CA, Almeida AM, Sanchez MA, Malpezzi EL, Costa LV, Hajdu E, De Freitas JC (1996) Chemical and pharmacological characterization of halitoxin from Amphimedon viridis (Porifera) from the southeastern Brazilian coast Comparative biochemistry and physiology Part C. Pharmacol Toxicol Endocrinol 115(2):155-163
59. Scott RH, Whyment AD, Foster A, Gordon KH, Milne BF, Jaspars M (2000) Analysis of the structure and electrophysiological actions of halitoxins: 1,3 alkyl-pyridinium salts from Callyspongia ridleyi. J Membr Biol 176(2):119-131
60. Sepcic K, Guella G, Mancini I, Pietra F, Serra MD, Menestrina G, Tubbs K, Macek P, Turk T (1997) Characterization of anticholinesterase-active 3-alkylpyridinium polymers from the marine sponge Reniera sarai in aqueous solutions. J Nat Prod 60(10):991-996
61. Davies-Coleman MT, Faulkner DJ, Dubowchik GM, Roth GP, Polson C, Fairchild C (1993) A New EGF-Active Polymeric Pyridinium Alkaloid from the Sponge Callyspongia fibrosa. J Org Chem 58:5925-5930
62. Koss DJ, Hindley KP, Riedel G, Platt B (2007) Modulation of hippocampal calcium signalling and plasticity by serine/threonine protein phosphatases. J Neurochem 102(4):1009-1023
63. Koss DJ, Riedel G, Platt B (2009) Intracellular Ca2 + stores modulate SOCCs and NMDA receptors via tyrosine kinases in rat hippocampal neurons. Cell Calcium 46(1):39-48
64. Scharschmidt BF, Lake JR, Renner EL, Licko V, van Dyke RW (1986) Fluid phase endocytosis by cultured rat hepatocytes and perfused rat liver: implications for plasma membrane turnover and vesicular trafficking of fluid phase markers. Proc Natl Acad Sci USA 83(24):9488-9492
65. Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch 391(2):85-100
66. Riedel G, Micheau J, Lam AG, Roloff EL, Martin SJ, Bridge H, de Hoz L, Poeschel B, McCulloch J, Morris RG (1999) Reversible neural inactivation reveals hippocampal participation in several memory processes. Nat Neurosci 2(10):898-905
67. Robinson L, McKillop-Smith S, Ross NL, Pertwee RG, Hampson RE, Platt B, Riedel G (2008) Hippocampal endocannabinoids inhibit spatial learning and limit spatial memory in rats. Psychopharmacology 198(4):551-563
68. Christie LA, Riedel G, Algaidi SA, Whalley LJ, Platt B (2005) Enhanced hippocampal long-term potentiation in rats after chronic exposure to homocysteine. Neurosci Lett 373(2):119-124
69. Koss DJ, Drever BD, Stoppelkamp S, Riedel G, Platt B (2013) Age-dependent changes in hippocampal synaptic transmission and plasticity in the PLB1(Triple) Alzheimer mouse. Cellular and molecular life sciences: CMLS 70(14):1273-1279
70. Algaidi SA, Christie LA, Jenkinson AM, Whalley L, Riedel G, Platt B (2006) Long-term homocysteine exposure induces alterations in spatial learning, hippocampal signalling and synaptic plasticity. Exp Neurol 197(1):8-21
71. Niewiadomska G, Baksalerska-Pazera M, Riedel G (2006) Cytoskeletal transport in the aging brain: focus on the cholinergic system. Rev Neurosci 17(6):581-618
72. Mudher AK, Perry VH (1998) Using okadaic acid as a tool for the in vivo induction of hyperphosphorylated Tau. Neuroscience 85(4):1329-1332
73. van Dam AM, Bol JG, Binnekade R, van Muiswinkel FL (1998) Acute or chronic administration of okadaic acid to rats induces brain damage rather than Alzheimer-like neuropathology. Neuroscience 85(4):1333-1335
74. Dayton RD, Wang DB, Cain CD, Schrott LM, Ramirez JJ, King MA, Klein RL (2012) Frontotemporal lobar degeneration-related proteins induce only subtle memory-related deficits when bilaterally overexpressed in the dorsal hippocampus. Exp Neurol 233(2):807-814
75. Yanamandra K, Kfoury N, Jiang H, Mahan TE, Ma S, Maloney SE, Wozniak DF, Diamond MI, Holtzman DM (2013) Anti-Tau antibodies that block Tau aggregate seeding in vitro markedly decrease pathology and improve cognition in vivo. Neuron 80(2):402-414
76. McLaggan D, Adjimatera N, Sepcic K, Jaspars M, Macewan DJ, Blagbrough IS, Scott RH (2006) Pore forming polyalkylpyridinium salts from marine sponges versus synthetic lipofection systems: distinct tools for intracellular delivery of cDNA and siRNA. BMC Biotechnol 6:6
77. Paleari L, Trombino S, Falugi C, Gallus L, Carlone S, Angelini C, Sepcic K, Turk T, Faimali M, Noonan DM, Albini A (2006) Marine sponge-derived polymeric alkylpyridinium salts as a novel tumor chemotherapeutic targeting the cholinergic system in lung tumors. Int J Oncol 29(6):1381-1388
78. Berne S, Pohleven F, Turk T, Sepcic K (2008) Induction of fruiting in oyster mushroom (Pleurotus ostreatus) by polymeric 3-alkylpyridinium salts. Mycol Res 112(Pt 9):1085-1087
79. Elersek T, Kosi G, Turk T, Pohleven F, Sepcic K (2008) Influence of polymeric 3-alkylpyridinium salts from the marine sponge Reniera sarai on the growth of algae and wood decay fungi. Biofouling 24(2):137-143
80. Grandic M, Araoz R, Molgo J, Turk T, Sepcic K, Benoit E, Frangez R (2013) Toxicity of the synthetic polymeric 3-alkylpyridinium salt (APS3) is due to specific block of nicotinic acetylcholine receptors. Toxicology 303:25-33
81. Turk T, Frangez R, Sepcic K (2007) Mechanisms of toxicity of 3-alkylpyridinium polymers from marine sponge Reniera sarai. Marine drugs 5(4):157-167
82. Yamada T, McGeer PL (1990) Oligodendroglial microtubular masses: an abnormality observed in some human neurodegenerative diseases. Neurosci Lett 120(2):163-166
83. Nishimura M, Tomimoto H, Suenaga T, Namba Y, Ikeda K, Akiguchi I, Kimura J (1995) Immunocytochemical characterization of glial fibrillary tangles in Alzheimer's disease brain. Am J Pathol 146(5):1052-1058
84. Bialojan C, Takai A (1988) Inhibitory effect of a marine-sponge toxin, okadaic acid, on protein phosphatases. Specificity and kinetics. The Biochemical journal 256(1):283-290
85. Cohen PT (1997) Novel protein serine/threonine phosphatases: variety is the spice of life. Trends Biochem Sci 22(7):245-251
86. Borthwick EB, Zeke T, Prescott AR, Cohen PT (2001) Nuclear localization of protein phosphatase 5 is dependent on the carboxy-terminal region. FEBS Lett 491(3):279-284
87. Malchiodi-Albedi F, Petrucci TC, Picconi B, Iosi F, Falchi M (1997) Protein phosphatase inhibitors induce modification of synapse structure and Tau hyperphosphorylation in cultured rat hippocampal neurons. J Neurosci Res 48(5):425-438
88. Kim D, Su J, Cotman CW (1999) Sequence of neurodegeneration and accumulation of phosphorylated Tau in cultured neurons after okadaic acid treatment. Brain Res 839(2):253-262
89. Tanaka T, Zhong J, Iqbal K, Trenkner E, Grundke-Iqbal I (1998) The regulation of phosphorylation of Tau in SY5Y neuroblastoma cells: the role of protein phosphatases. FEBS Lett 426(2):248-254
90. Furukawa K, Wang Y, Yao PJ, Fu W, Mattson MP, Itoyama Y, Onodera H, D'Souza I, Poorkaj PH, Bird TD, Schellenberg GD (2003) Alteration in calcium channel properties is responsible for the neurotoxic action of a familial frontotemporal dementia Tau mutation. J Neurochem 87(2):427-436
91. Stoppelkamp S, Bell HS, Palacios-Filardo J, Shewan DA, Riedel G, Platt B (2011) In vitro modelling of Alzheimer's disease: degeneration and cell death induced by viral delivery of amyloid and Tau. Exp Neurol 229(2):226-237
92. Zempel H, Mandelkow E (2014) Lost after translation: missorting of Tau protein and consequences for Alzheimer disease. Trends Neurosci 37(12):721-732
93. Duff K, Knight H, Refolo LM, Sanders S, Yu X, Picciano M, Malester B, Hutton M, Adamson J, Goedert M, Burki K, Davies P (2000) Characterization of pathology in transgenic mice over-expressing human genomic and cDNA Tau transgenes. Neurobiology of disease 7(2):87-98
94. Andorfer C, Kress Y, Espinoza M, de Silva R, Tucker KL, Barde YA, Duff K, Davies P (2003) Hyperphosphorylation and aggregation of Tau in mice expressing normal human Tau isoforms. J Neurochem 86(3):582-590
95. Polydoro M, Acker CM, Duff K, Castillo PE, Davies P (2009) Age-dependent impairment of cognitive and synaptic function in the htau mouse model of Tau pathology. The Journal of neuroscience: the official journal of the Society for Neuroscience 29(34):10741-10749
96. Khandelwal PJ, Dumanis SB, Herman AM, Rebeck GW, Moussa CE (2012) Wild type and P301L mutant Tau promote neuro-inflammation and alpha-Synuclein accumulation in lentiviral gene delivery models. Molecular and cellular neurosciences 49(1):44-53
97. Dayton RD, Wang DB, Cain CD, Schrott LM, Ramirez JJ, King MA, Klein RL (2012) Frontotemporal lobar degeneration-related proteins induce only subtle memory-related deficits when bilaterally overexpressed in the dorsal hippocampus. Exp Neurol 233(2):807-814
98. Caillierez R, Begard S, Lecolle K, Deramecourt V, Zommer N, Dujardin S, Loyens A, Dufour N, Auregan G, Winderickx J, Hantraye P, Deglon N, Buee L, Colin M (2013) Lentiviral delivery of the human wild-type Tau protein mediates a slow and progressive neurodegenerative Tau pathology in the rat brain. Molecular therapy: the journal of the American Society of Gene Therapy 21(7):1358-1368
99. Dujardin S, Lecolle K, Caillierez R, Begard S, Zommer N, Lachaud C, Carrier S, Dufour N, Auregan G, Winderickx J, Hantraye P, Deglon N, Colin M, Buee L (2014) Neuron-to-neuron wild-type Tau protein transfer through a trans-synaptic mechanism relevance to sporadic tauopathies. Acta Neuropathol Commun 2:14
100. He J, Yamada K, Zou LB, Nabeshima T (2001) Spatial memory deficit and neurodegeneration induced by the direct injection of okadaic acid into the hippocampus in rats. J Neural Transm Vienna Austria 108(12):1435-1443
101. Sun L, Liu SY, Zhou XW, Wang XC, Liu R, Wang Q, Wang JZ (2003) Inhibition of protein phosphatase 2A- and protein phosphatase 1-induced Tau hyperphosphorylation and impairment of spatial memory retention in rats. Neuroscience 118(4):1175-1182
102. He J, Yang Y, Xu H, Zhang X, Li XM (2005) Olanzapine attenuates the okadaic acid-induced spatial memory impairment and hippocampal cell death in rats. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 30(8):1511-1520
103. Arendt T, Holzer M, Fruth R, Bruckner MK, Gartner U (1995) Paired helical filament-like phosphorylation of Tau, deposition of beta/A4-amyloid and memory impairment in rat induced by chronic inhibition of phosphatase 1 and 2A. Neuroscience 69(3):691-698
104. Millward TA, Zolnierowicz S, Hemmings BA (1999) Regulation of protein kinase cascades by protein phosphatase 2A. Trends Biochem Sci 24(5):186-191
105. Herzig S, Neumann J (2000) Effects of serine/threonine protein phosphatases on ion channels in excitable membranes. Physiol Rev 80(1):173-210
106. Zhang Z, Simpkins JW (2010) An okadaic acid-induced model of tauopathy and cognitive deficiency. Brain Res 1359:233-246
107. Khatoon S, Grundke-Iqbal I, Iqbal K (1992) Brain levels of microtubule-associated protein Tau are elevated in Alzheimer's disease: a radioimmuno-slot-blot assay for nanograms of the protein. J Neurochem 59(2):750-753
108. Khatoon S, Grundke-Iqbal I, Iqbal K (1994) Levels of normal and abnormally phosphorylated Tau in different cellular and regional compartments of Alzheimer disease and control brains. FEBS Lett 351(1):80-84
109. Holzer M, Holzapfel HP, Zedlick D, Bruckner MK, Arendt T (1994) Abnormally phosphorylated Tau protein in Alzheimer's disease: heterogeneity of individual regional distribution and relationship to clinical severity. Neuroscience 63(2):499-516
110. Thal DR, Holzer M, Rub U, Waldmann G, Gunzel S, Zedlick D, Schober R (2000) Alzheimer-related Tau-pathology in the perforant path target zone and in the hippocampal stratum oriens and radiatum correlates with onset and degree of dementia. Exp Neurol 163(1):98-110
111. Wang X, Zhu M, Hjorth E, Cortes-Toro V, Eyjolfsdottir H, Graff C, Nennesmo I, Palmblad J, Eriksdotter M, Sambamurti K, Fitzgerald JM, Serhan CN, Granholm AC, Schultzberg M (2015) Resolution of inflammation is altered in Alzheimer's disease. Alzheimer's Dement J Alzheimer's Assoc 11(1):40-50
112. Bancher C, Braak H, Fischer P, Jellinger KA (1993) Neuropathological staging of Alzheimer lesions and intellectual status in Alzheimer's and Parkinson's disease patients. Neurosci Lett 162(1-2):179-182
113. Freedman M, Oscar-Berman M (1989) Spatial and visual learning deficits in Alzheimer's and Parkinson's disease. Brain Cogn 11(1):114-126
114. Gold CA, Budson AE (2008) Memory loss in Alzheimer's disease: implications for development of therapeutics. Expert Rev Neurother 8(12):1879-1891
115. Whitlock JR, Heynen AJ, Shuler MG, Bear MF (2006) Learning induces long-term potentiation in the hippocampus. Science (New York, NY) 313(5790):1093-1097
116. Nabavi S, Fox R, Proulx CD, Lin JY, Tsien RY, Malinow R (2014) Engineering a memory with LTD and LTP. Nature 511(7509):348-352
117. Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, Metherate R, Mattson MP, Akbari Y, Laferla FM (2003) Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 39(3):409-421
118. Rosenmann H, Grigoriadis N, Eldar-Levy H, Avital A, Rozenstein L, Touloumi O, Behar L, Ben-Hur T, Avraham Y, Berry E, Segal M, Ginzburg I, Abramsky O (2008) A novel transgenic mouse expressing double mutant Tau driven by its natural promoter exhibits tauopathy characteristics. Exp Neurol 212(1):71-84
119. Lo AC, Iscru E, Blum D, Tesseur I, Callaerts-Vegh Z, Buee L, de Strooper B, Balschun D, D'Hooge R (2013) Amyloid and Tau neuropathology differentially affect prefrontal synaptic plasticity and cognitive performance in mouse models of Alzheimer's disease. J Alzheimer's Dis JAD 37(1):109-125
120. Platt B, Drever B, Koss D, Stoppelkamp S, Jyoti A, Plano A, Utan A, Merrick G, Ryan D, Melis V, Wan H, Mingarelli M, Porcu E, Scrocchi L, Welch A, Riedel G (2011) Abnormal cognition, sleep, EEG and brain metabolism in a novel knock-in Alzheimer mouse, PLB1. PLoS One 6(11):e27068
121. Ryan D, Koss D, Porcu E, Woodcock H, Robinson L, Platt B, Riedel G (2013) Spatial learning impairments in PLB1Triple knock-in Alzheimer mice are task-specific and age-dependent. Cell Mol life Sci CMLS 70(14):2603-2619
122. Robinson L, Goonawardena AV, Pertwee RG, Hampson RE, Riedel G (2007) The synthetic cannabinoid HU210 induces spatial memory deficits and suppresses hippocampal firing rate in rats. Br J Pharmacol 151(5):688-700
123. Robinson L, Goonawardena AV, Pertwee R, Hampson RE, Platt B, Riedel G (2010) WIN55,212-2 induced deficits in spatial learning are mediated by cholinergic hypofunction. Behav Brain Res 208(2):584-592
124. Houssen WE, Lu Z, Edrada-Ebel R, Chatzi C, Tucker SJ, Sepcic K, Turk T, Zovko A, Shen S, Mancini I, Scott RH, Jaspars M (2010) Chemical synthesis and biological activities of 3-alkyl pyridinium polymeric analogues of marine toxins. J Chem Biol 3(3):113-125
125. Paxinos G, Watson C (2013) The Rat Brain in stereotaxic coordinates, 7th edn. Academic Press, London