Skip to main content

Advertisement

SpringerLink
Log in

Neurotoxic dopamine quinone facilitates the assembly of tau into fibrillar polymers

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Aberrant aggregation of microtubule associated protein tau is the main characteristic of different disorders known as tauopathies. Different compounds have been described to facilitate tau aberrant aggregation. In this work, we demonstrate that oxidized products of dopamine (neurotoxic dopamine quinone), a neurotransmitter involved in Parkinson's disease, promote tau polymerization. Curiously, neurons expressing dopamine (substantia nigra) show a low content of tau protein and seldom have tau aggregation in tauopathies. In non-dopaminergic neurons, quinone oxidation products may be involved in tau polymerization. These results support a link between oxidative damage and the onset of tauopathies. (Mol Cell Biochem 278: 203–212, 2005)

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI: Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA 83: 4913–4917, 1986

    PubMed  Google Scholar 

  2. Goedert M: Filamentous nerve cell inclusions in neurodegenerative diseases: tauopathies and alpha-synucleinopathies. Philos Trans R Soc Lond B Biol Sci 354: 1101–1118, 1999

    Article  PubMed  Google Scholar 

  3. Gamblin TC, Berry RW, Binder LI: Tau polymerization: Role of the amino terminus. Biochemistry 42: 2252–2257, 2003

    Article  PubMed  Google Scholar 

  4. Goedert M, Jakes R, Spillantini MG, Hasegawa M, Smith MJ, Crowther RA: Assembly of microtubule-associated protein tau into Alzheimer-like filaments induced by sulphated glycosaminoglycans. Nature 383: 550–553, 1996

    Article  PubMed  Google Scholar 

  5. Perez M, Valpuesta JM, Medina M, Montejo de Garcini E, Avila J: Polymerization of tau into filaments in the presence of heparin: The minimal sequence required for tau-tau interaction. J Neurochem 67: 1183–1190, 1996

    PubMed  Google Scholar 

  6. Kampers T, Friedhoff P, Biernat J, Mandelkow EM, Mandelkow E: RNA stimulates aggregation of microtubule-associated protein tau into Alzheimer-like paired helical filaments. FEBS Lett 399: 344–349, 1996

    Article  PubMed  Google Scholar 

  7. Gamblin TC, King ME, Kuret J, Berry RW, Binder LI: Oxidative regulation of fatty acid-induced tau polymerization. Biochemistry 39: 14203–14210, 2000

    Article  PubMed  Google Scholar 

  8. Perez M, Cuadros R, Smith MA, Perry G, Avila J: Phosphorylated, but not native, tau protein assembles following reaction with the lipid peroxidation product, 4-hydroxy-2-nonenal. FEBS Lett 486: 270–274, 2000

    Article  PubMed  Google Scholar 

  9. Wilson DM, Binder LI: Free fatty acids stimulate the polymerization of tau and amyloid beta peptides. In vitro evidence for a common effector of pathogenesis in Alzheimer’s disease. Am J Pathol 150: 2181–2195, 1997

    PubMed  Google Scholar 

  10. Ames BN: Mitochondrial decay, a major cause of aging, can be delayed. J Alzheimers Dis 6: 117–121, 2004

    PubMed  Google Scholar 

  11. Mitchell P: The vital protonmotive role of coenzyme Q. In: Folkers K, Littarru GP, Yamamura T (eds). Biomedical and Clinical Aspects of Coenzyme Q, Vol. 6, Elsevier, Amsterdam, 1991, pp 3–10

  12. Larsen PL, Clarke CF: Extension of life-span in Caenorhabditis elegans by a diet lacking coenzyme Q. Science 295: 120–123, 2002

    Article  PubMed  Google Scholar 

  13. Tatar M, Rand DM: Aging. Dietary advice on Q. Science 295: 54–55, 2002

    Google Scholar 

  14. Santa-Maria I, Hernandez F, Martin CP, Avila J, Moreno FJ: Quinones facilitate the self-assembly of the phosphorylated tubulin binding region of tau into fibrillar polymers. Biochemistry 43: 2888–2897, 2004

    Article  PubMed  Google Scholar 

  15. Smith MA, Sayre LM, Vitek MP, Monnier VM, Perry G: Early AGEing and Alzheimer’s. Nature 374: 316, 1995

    Google Scholar 

  16. Perez RG, Waymire JC, Lin E, Liu JJ, Guo F, Zigmond MJ: A role for alpha-synuclein in the regulation of dopamine biosynthesis. J Neurosci 22: 3090–3099, 2002

    PubMed  Google Scholar 

  17. Linert W, Jameson GN: Redox reactions of neurotransmitters possibly involved in the progression of Parkinson’s disease. J Inorg Biochem 79: 319–326, 2000

    Article  PubMed  Google Scholar 

  18. Conway KA, Rochet JC, Bieganski RM, Lansbury PT, Jr: Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct. Science 294: 1346–1349, 2001

    Article  PubMed  Google Scholar 

  19. Pérez Martín C, Vázquez J, Avila J, Moreno FJ: P24, a glycogen synthase kinase 3 (GSK 3) inhibitor. Biochim Biophys Acta 1586: 113–122, 2002

    PubMed  Google Scholar 

  20. Moreno FJ, Medina M, Perez M, Montejo de Garcini E, Avila J: Glycogen synthase kinase 3 phosphorylates recombinant human tau protein at serine-262 in the presence of heparin (or tubulin). FEBS Lett 372: 65–68, 1995

    Article  PubMed  Google Scholar 

  21. Medina M, Montejo de Garcini E, Avila J: The role of tau phosphorylation in transfected COS-1 cells. Mol Cell Biochem 148: 79–88, 1995

    Article  PubMed  Google Scholar 

  22. Goedert M, Jakes R: Expression of separate isoforms of human tau protein: Correlation with the tau pattern in brain and effects on tubulin polymerization. EMBO J 9: 4225–4230, 1990

    PubMed  Google Scholar 

  23. Moreno FJ, Avila J: Phosphorylation of stathmin modulates its function as a microtubule depolymerizing factor. Mol Cell Biochem 183: 201–209, 1998

    Article  PubMed  Google Scholar 

  24. Crowther RA, Olesen OF, Smith MJ, Jakes R, Goedert M: Assembly of Alzheimer-like filaments from full-length tau protein. FEBS Lett 337: 135–138, 1994

    Article  PubMed  Google Scholar 

  25. Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680–685, 1970

    PubMed  Google Scholar 

  26. Lucas JJ, Hernandez F, Gomez-Ramos P, Moran MA, Hen R, Avila J: Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice. EMBO J 20: 27–39, 2001

    Article  PubMed  Google Scholar 

  27. Novak M, Jakes R, Edwards PC, Milstein C, Wischik CM: Difference between the tau protein of Alzheimer paired helical filament core and normal tau revealed by epitope analysis of monoclonal antibodies 423 and 7.51. Proc Natl Acad Sci USA 88: 5837–5841, 1991

    PubMed  Google Scholar 

  28. Biedler JL, Roffler-Tarlov S, Schachner M, Freedman LS: Multiple neurotransmitter synthesis by human neuroblastoma cell lines and clones. Cancer Res 38: 3751–3757, 1978

    PubMed  Google Scholar 

  29. Greenberg SG, Davies P: A preparation of Alzheimer paired helical filaments that displays distinct tau proteins by polyacrylamide gel electrophoresis. Proc Natl Acad Sci USA 87: 5827–5831, 1990

    PubMed  Google Scholar 

  30. Zecca L, Zucca FA, Wilms H, Sulzer D: Neuromelanin of the substantia nigra: a neuronal black hole with protective and toxic characteristics. Trends Neurosci 26: 578–580, 2003

    Article  PubMed  Google Scholar 

  31. Clark LN, Poorkaj P, Wszolek Z, Geschwind DH, Nasreddine ZS, Miller B, Li D, Payami H, Awert F, Markopoulou K, Andreadis A, D’Souza I, Lee VM, Reed L, Trojanowski JQ, Zhukareva V, Bird T, Schellenberg G, Wilhelmsen KC: Pathogenic implications of mutations in the tau gene in pallido-ponto-nigral degeneration and related neurodegenerative disorders linked to chromosome 17. Proc Natl Acad Sci USA 95: 13103–13107, 1998

    Article  PubMed  Google Scholar 

  32. Avila J, Lucas JJ, Perez M, Hernandez F: Role of tau protein in both physiological and pathological conditions. Physiol Rev 84: 361–384, 2004

    Article  PubMed  Google Scholar 

  33. Garcia-Perez J, Avila J, Diaz-Nido J: Implication of cyclin-dependent kinases and glycogen synthase kinase 3 in the phosphorylation of microtubule-associated protein 1B in developing neuronal cells. J Neurosci Res 52: 445–452, 1998

    Article  PubMed  Google Scholar 

  34. Duda JE, Giasson BI, Mabon ME, Miller DC, Golbe LI, Lee VM, Trojanowski JQ: Concurrence of alpha-synuclein and tau brain pathology in the Contursi kindred. Acta Neuropathol (Berl) 104: 7–11, 2002

    Article  Google Scholar 

  35. Giasson BI, Forman MS, Higuchi M, Golbe LI, Graves CL, Kotzbauer PT, Trojanowski JQ, Lee VM: Initiation and synergistic fibrillization of tau and alpha-synuclein. Science 300: 636–640, 2003

    Article  PubMed  Google Scholar 

  36. Galloway PG, Bergeron C, Perry G: The presence of tau distinguishes Lewy bodies of diffuse Lewy body disease from those of idiopathic Parkinson disease. Neurosci Lett 100: 6–10, 1989

    PubMed  Google Scholar 

  37. Perez M, Valpuesta JM, de Garcini EM, Quintana C, Arrasate M, Lopez Carrascosa JL, Rabano A, Garcia de Yebenes J, Avila J: Ferritin is associated with the aberrant tau filaments present in progressive supranuclear palsy. Am J Pathol 152: 1531–1539, 1998

    PubMed  Google Scholar 

  38. Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj EK, Jones PK, Ghanbari H, Wataya T, Shimohama S, Chiba S, Atwood CS, Petersen RB, Smith MA: Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 60: 759–767, 2001

    PubMed  Google Scholar 

  39. Raina AK, Templeton DJ, Deak JC, Perry G, Smith MA: Quinone reductase (NQO1), a sensitive redox indicator, is increased in Alzheimer’s disease. Redox Rep 4: 23–27, 1999

    Article  PubMed  Google Scholar 

  40. Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R: A C. elegans mutant that lives twice as long as wild type. Nature 366: 461–464, 1993

    Google Scholar 

  41. Dillin A, Crawford DK, Kenyon C: Timing requirements for insulin/IGF-1 signaling in C. elegans. Science 298: 830–834, 2002

    Article  PubMed  Google Scholar 

  42. Tatar M, Bartke A, Antebi A: The endocrine regulation of aging by insulin-like signals. Science 299: 1346–1351, 2003

    Article  PubMed  Google Scholar 

  43. Longo VD, Fabrizio P: Regulation of longevity and stress resistance: A molecular strategy conserved from yeast to humans? Cell Mol Life Sci 59: 903–908, 2002

    Article  PubMed  Google Scholar 

  44. Boirie Y: Insulin regulation of mitochondrial proteins and oxidative phosphorylation in human muscle. Trends Endocrinol Metab 14: 393–394, 2003

    Article  PubMed  Google Scholar 

  45. Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, Johnson AB, Kress Y, Vinters HV, Tabaton M, Shimohama S, Cash AD, Siedlak SL, Harris PL, Jones PK, Petersen RB, Perry G, Smith MA: Mitochondrial abnormalities in Alzheimer’s disease. J Neurosci 21: 3017–3023, 2001

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centro de Biología Molecular “Severo Ochoa”, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain

    Ismael Santa-María, Félix Hernández, Jesús Avila & Francisco J. Moreno

  2. Institute of Pathology, Case Western Reserve University, Cleveland, Ohio, USA

    Mark A. Smith & George Perry

  3. Centro de Biología Molecular “Severo Ochoa”, Facultad de Ciencias, Campus de Cantoblanco, Universidad Autónoma de Madrid, Madrid, 28049, Spain

    Jesús Avila

Authors
  1. Ismael Santa-María
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Félix Hernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mark A. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. George Perry
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jesús Avila
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Francisco J. Moreno
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jesús Avila.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Santa-María, I., Hernández, F., Smith, M.A. et al. Neurotoxic dopamine quinone facilitates the assembly of tau into fibrillar polymers. Mol Cell Biochem 278, 203–212 (2005). https://doi.org/10.1007/s11010-005-7499-6

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-005-7499-6

Key Word

Search

Navigation