Cell Models of Tauopathy

  • J. Biernat
  • I. Khlistunova
  • Y-P. Wang
  • M. Pickhardt
  • M. von Bergen
  • Z. Gazova
  • Eckhart Mandelkow
  • Eva-Marie Mandelkow
Part of the Advances in Behavioral Biology book series (ABBI, volume 57)


Repeat Domain Paired Helical Filament KXGS Motif Hexapeptide Motif Antibody K9JA 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Lee VM, Goedert M, Trojanowski JQ. Neurodegenerative tauopathies. Annu Rev Neurosci 2001;24:1121–1159.PubMedCrossRefGoogle Scholar
  2. 2.
    Coleman PD, Yao PJ. Synaptic slaughter in Alzheimer's disease. Neurobiol Aging 2003;24:1023–1027.PubMedCrossRefGoogle Scholar
  3. 3.
    Terwel D, Lasrado R, Snauwaert J, et al. Changed conformation of mutant tau-P301L underlies the moribund tauopathy, absent in progressive, nonlethal axonopathy of tau-4R/2N transgenic mice. J Biol Chem 2005;280:3963–3973.PubMedCrossRefGoogle Scholar
  4. 4.
    Lewis J, Dickson DW, Lin WL, et al. Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science 2001;293:1487–1491.PubMedCrossRefGoogle Scholar
  5. 5.
    Gotz J, Chen F, van Dorpe J, Nitsch RM. Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils. Science 2001;293:1491–1495.PubMedCrossRefGoogle Scholar
  6. 6.
    Oddo S, Caccamo A, Shepherd JD, et al. Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 2003;39:409–421.PubMedCrossRefGoogle Scholar
  7. 7.
    Vogelsberg-Ragaglia V, Bruce J, Richter-Landsberg C, et al. Distinct FTDP-17 mis-sense mutations in tau produce tau aggregates and other pathological phenotypes in transfected CHO cells. Mol Biol Cell 2000;11:4093–4104.PubMedGoogle Scholar
  8. 8.
    DeTure M, Ko LW, Easson C, Yen SH. Tau assembly in inducible transfectants expressing wild-type or FTDP-17 tau. Am J Pathol 2002;161:1711–1722.PubMedGoogle Scholar
  9. 9.
    Ferrari A, Hoerndli F, Baechi T, et al. Beta-amyloid induces paired helical filament-like tau filaments in tissue culture. J Biol Chem 2003;278:40162–40168.PubMedCrossRefGoogle Scholar
  10. 10.
    Santacruz K, Lewis J, Spires T, et al. Tau suppression in a neurodegenerative mouse model improves memory function. Science 2005;309:476–481.PubMedCrossRefGoogle Scholar
  11. 11.
    LaFerla FM, Oddo S. Alzheimer's disease: Abeta, tau and synaptic dysfunction. Trends Mol Med 2005;11:170–176.PubMedCrossRefGoogle Scholar
  12. 12.
    Ashe KH. Mechanisms of memory loss in Abeta and tau mouse models. Biochem Soc Trans 2005;33:591–594.PubMedCrossRefGoogle Scholar
  13. 13.
    Khlistunova I, Biernat J, Wang Y, et al. Inducible expression of tau repeat domain in cell models of tauopathy: aggregation is toxic to cells but can be reversed by inhibitor drugs. J Biol Chem 2006;281:1205–1214.PubMedCrossRefGoogle Scholar
  14. 14.
    Gossen M, Bujard H. Studying gene function in eukaryotes by conditional gene inactivation. Annu Rev Genet 2002;36:153–173.PubMedCrossRefGoogle Scholar
  15. 15.
    Von Bergen M, Barghorn S, Li L, et al. Mutations of tau protein in fronto-temporal dementia promote aggregation of paired helical filaments by enhancing local beta- structure. J Biol Chem 2001;276:48165–48174.Google Scholar
  16. 16.
    Wille H, Drewes G, Biernat J, et al. Alzheimer-like paired helical filaments and antiparallel dimers formed from microtubule-associated protein tau in vitro. J Cell Biol 1992;118:573–584.PubMedCrossRefGoogle Scholar
  17. 17.
    Barghorn S, Zheng-Fischhofer Q, Ackmann M, et al. Structure, microtubule interactions, and paired helical filament aggregation by tau mutants of fronto-temporal dementias. Biochemistry 2000;39:11714–11721.PubMedCrossRefGoogle Scholar
  18. 18.
    Rosso SM, van Swieten JC. New developments in frontotemporal dementia and parkinsonism linked to chromosome 17. Curr Opin Neurol 2002;5:423–428.CrossRefGoogle Scholar
  19. 19.
    D'Souza I, Schellenberg GD. Regulation of tau isoform expression and dementia. Biochim Biophys Acta 2005;1739:104–115.PubMedGoogle Scholar
  20. 20.
    Von Bergen M, Friedhoff P, Biernat J, et al. Assembly of tau protein into Alzheimer paired helical filaments depends on a local sequence motif ([306]VQIVYK[311]) forming beta structure. Proc Natl Acad Sci U S A 2000;97:5129–5133.CrossRefGoogle Scholar
  21. 21.
    Urlinger S, Baron U, Thellmann M, et al. Exploring the sequence space for tetracycline-dependent transcriptional activators: novel mutations yield expanded range and sensitivity. Proc Natl Acad Sci U S A 2000;97:7963–7968.PubMedCrossRefGoogle Scholar
  22. 22.
    Bunker JM, Wilson L, Jordan MA, Feinstein SC. Modulation of microtubule dynamics by tau in living cells: implications for development and neurodegeneration. Mol Biol Cell 2004;15:2720–2728.PubMedCrossRefGoogle Scholar
  23. 23.
    Stamer K, Vogel R, Thies E, et al. Tau blocks traffic of organelles, neurofilaments, and APP vesicles in neurons and enhances oxidative stress. J Cell Biol 2002;156:1051–1063.PubMedCrossRefGoogle Scholar
  24. 24.
    Mandelkow EM, Thies E, Trinczek B, et al. MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons. J Cell Biol 2004;167:99–110.PubMedCrossRefGoogle Scholar
  25. 25.
    Pickhardt M, Gazova Z, von Bergen M, et al. Anthraquinones inhibit tau aggregation and dissolve Alzheimer's paired helical filaments in vitro and in cells. J Biol Chem 2005;280:3628–3635.PubMedCrossRefGoogle Scholar
  26. 26.
    Greenberg SG, Davies P. Preparation of Alzheimer paired helical filaments that display distinct tau proteins by polyacrylamide gel electrophoresis. Proc Natl Acad Sci U S A 1990;87:5827–5831.PubMedCrossRefGoogle Scholar
  27. 27.
    Watanabe A, Hong WK, Dohmae N, et al. Molecular aging of tau: disulfide-independent aggregation and non-enzymatic degradation in vitro and in vivo. J Neurochem 2004;90:1302–1311.PubMedCrossRefGoogle Scholar
  28. 28.
    Schneider A, Biernat J, von Bergen M, et al. Phosphorylation that detaches tau protein from microtubules (Ser262, Ser214) also protects it against aggregation into Alzheimer paired helical filaments. Biochemistry 1999;38:3549–3558.PubMedCrossRefGoogle Scholar
  29. 29.
    Arai T, Guo JP, McGeer PL. Proteolysis of non-phosphorylated and phosphorylated tau by thrombin. J Biol Chem 2005;280:5145–5153.PubMedCrossRefGoogle Scholar
  30. 30.
    Binder LI, Guillozet-Bongaarts AL, Garcia-Sierra F, Berry RW. Tau, tangles, and Alzheimer's disease. Biochim Biophys Acta 2005;1739:216–223.PubMedGoogle Scholar
  31. 31.
    Perez M, Hernandez F, Gomez-Ramos A, et al. Formation of aberrant phosphotau fibrillar polymers in neural cultured cells. Eur J Biochem 2002;269:1484–1489.PubMedCrossRefGoogle Scholar
  32. 32.
    Drewes G, Ebneth A, Preuss U, et al. MARK, a novel family of protein kinases that phosphorylate microtubule-associated proteins and trigger microtubule disruption. Cell 1997;89:297–308.PubMedCrossRefGoogle Scholar
  33. 33.
    Mukrasch MD, Biernat J, von Bergen M, et al. Sites of tau important for aggregation populate beta-structure and bind to microtubules and polyanions. J Biol Chem 2005;280:24978–24986.PubMedCrossRefGoogle Scholar
  34. 34.
    Lambert MP, Barlow AK, Chromy BA, et al. Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. Proc Natl Acad Sci U S A 1998;95:6448–6453.PubMedCrossRefGoogle Scholar
  35. 35.
    Walsh DM, Klyubin I, Fadeeva JV, et al. Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 2002;416:535–539.PubMedCrossRefGoogle Scholar
  36. 36.
    Bucciantini M, Giannoni E, Chiti F, et al. Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases. Nature 2002;416:507–511.PubMedCrossRefGoogle Scholar
  37. 37.
    David DC, Layfield R, Serpell L, et al. Proteasomal degradation of tau protein. J Neurochem 2002;83:176–185.PubMedCrossRefGoogle Scholar
  38. 38.
    Kosik KS, Shimura H. Phosphorylated tau and the neurodegenerative foldopathies. Biochim Biophys Acta 2005;1739:298–310.PubMedGoogle Scholar
  39. 39.
    Delobel P, Leroy O, Hamdane M, et al. Proteasome inhibition and tau proteolysis: an unexpected regulation. FEBS Lett 2005;579:1–5.PubMedCrossRefGoogle Scholar
  40. 40.
    Brown MR, Bondada V, Keller JN, et al. Proteasome or calpain inhibition does not alter cellular tau levels in neuroblastoma cells or primary neurons. J Alzheimers Dis 2005;7:15–24.PubMedGoogle Scholar
  41. 41.
    Nixon RA, Wegiel J, Kumar A, et al. Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. Neuropathol Exp Neurol 2005;64:113–122.Google Scholar
  42. 42.
    Li L, von Bergen M, Mandelkow EM, Mandelkow E. Structure, stability, and aggregation of paired helical filaments from tau protein and FTDP-17 mutants probed by tryptophan scanning mutagenesis. J Biol Chem 2002;277:41390–41400.PubMedCrossRefGoogle Scholar
  43. 43.
    Chirita C, Necula M, Kuret J. Ligand-dependent inhibition and reversal of tau filament formation. Biochemistry 2004;43:2879–2887.PubMedCrossRefGoogle Scholar
  44. 44.
    Taniguchi S, Suzuki N, Masuda M, et al. Inhibition of heparin-induced tau filament formation by phenothiazines, polyphenols, and porphyrins. J Biol Chem 2005;280:7614–7623.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • J. Biernat
    • 1
  • I. Khlistunova
  • Y-P. Wang
  • M. Pickhardt
  • M. von Bergen
  • Z. Gazova
  • Eckhart Mandelkow
  • Eva-Marie Mandelkow
  1. 1.Max-Planck-Unit for Structural Molecular Biologyc/o DESYGermany

Personalised recommendations