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Cited by 379Alzheimer's disease research and treatmentsAmyotrophic Lateral Sclerosis ResearchNeuroinflammation and Neurodegeneration Mechanisms

Neurodegeneration and defective neurotransmission in a Caenorhabditis elegans model of tauopathy

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Kraemer, Brian C., Zhang, Bin, Leverenz, James B., Thomas, James H., Trojanowski, John Q., Schellenberg, Gerard D.·2003·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1533448100PMC PMC187908
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Abstract

Frontotemporal dementia with parkinsonism chromosome 17 type (FTDP-17) is caused by mutations in MAPT , the gene encoding tau. FTDP-17 begins with executive function deficits and other abnormal behaviors, which progress to dementia. Neurodegenerative changes include accumulation of aggregated tau as neuronal and glial fibrillary tangles. Aggregated tau is seen in numerous other neurodegenerative diseases, including Alzheimer's disease (AD). We expressed normal and FTDP-17 mutant human tau (mutations P 301 L and V 337 M ) in Caenorhabditis elegans to model tauopathy disorders. Tau pan-neuronal expression caused progressive uncoordinated locomotion (Unc), characteristic of nervous system defects in worms. Subsequently, insoluble tau accumulates and both soluble and insoluble tau is phosphorylated at many of the sites hyperphosphorylated in FTDP-17, AD, and other tauopathies. Substantial neurodegeneration, seen as bulges and gaps in nerve cords followed by loss of neurons, occurs after insoluble tau begins to accumulate. Axons show vacuoles, membranous infoldings, and whorls with associated amorphous tau accumulations and abnormal tau-positive aggregates. FTDP-17 mutation lines had a more severe Unc phenotype, accumulated more insoluble tau at a younger age, were more resistant to cholinergic inhibitors, and had more severe axonal degeneration when compared with lines expressing normal tau. The Unc phenotype is caused by a presynaptic defect. Postsynaptic transmission is intact. This transgenic model will enable mechanistic dissection of tau-induced neurodegeneration and identification of genes and compounds that inhibit pathological tau formation.

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  • Several invertebrate and vertebrate transgenic animal models have shown that tau can induce neurodegeneration and apoptosis.

    “Several invertebrate and vertebrate transgenic animal models have shown that tau can induce neurodegeneration and apoptosis (43–46).”

    From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [46]

    The Abstract reports age-dependent loss of axons and neurons in transgenic C. elegans expressing tau. The Discussion also describes neurodegeneration in Drosophila and mouse tau models. Neither passage establishes apoptosis, so that part of the claim is unsupported. (LLM, conf=0.87)

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Research works printed but not linked: 37

  1. [1]Hutton, M., Lendon, C. L., Rizzu, P., Baker, M., Froelich, S., Houlden, H., Pickering-Brown, S., Chakraverty, S., Isaacs, A., Grover, A., et al. (1998) Nature 393, 702–705. [DOI] [PubMed] [Google Scholar]
  2. [2]Poorkaj, P., Bird, T. D., Wijsman, E., Nemens, E., Garruto, R. M., Anderson, L., Andreadis, A., Wiederholt, W. C., Raskind, M. & Schellenberg, C. D. (1998) Ann. Neurol. 43, 815–825. [DOI] [PubMed] [Google Scholar]
  3. [3]Spillantini, M. G., Murrell, J. R., Goedert, M., Farlow, M. R., Klug, A. & Ghetti, B. (1998) Proc. Natl. Acad. Sci. USA 95, 7737–7741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. [4]Hong, M., Zhukareva, V., Vogelsberg-Ragaglia, V., Wszolek, Z., Reed, L., Miller, B. I., Geschwind, D. H., Bird, T. D., McKeel, D. Goate, A., et al. (1998) Science 282, 1914–1917. [DOI] [PubMed] [Google Scholar]
  5. [5]Goedert, M., Jakes, R. & Crowther, R. A. (1999) FEBS Lett. 450, 306–311. [DOI] [PubMed] [Google Scholar]
  6. [6]Nacharaju, P., Lewis, J., Easson, C., Yen, S., Hackett, J., Hutton, M. & Yen, S. H. (1999) FEBS Lett. 447, 195–199. [DOI] [PubMed] [Google Scholar]
  7. [7]Buee, L., Bussiere, T., Buee-Scherrer, V., Delacourte, A. & Hof, P. R. (2000) Brain Res. Rev. 33, 95–130. [DOI] [PubMed] [Google Scholar]
  8. [8]K. Iwasaki, K., Staunton, J., Saifee, O., Nonet, M. & Thomas, J. H. (1997) Neuron 18, 613–622. [DOI] [PubMed] [Google Scholar]
  9. [9]Taub, J., Lau, J. F., Ma, C., Hahn, J. H., Hoque, R., Rothblatt, J. & Chalfie, M. (1999) Nature 399, 162–166. [DOI] [PubMed] [Google Scholar]
  10. [10]Ishihara, T., Hong, M., Zhang, B., Nakagawa, Y., Lee, M. K., Trojanowski, J. Q. & Lee, V. M. Y. (1999) Neuron 24, 751–762. [DOI] [PubMed] [Google Scholar]
  11. [11]Harlowe, E. & Lane, D. (1999) in Using Antibodies: A Laboratory Manual (Cold Spring Harbor Lab. Press, Plainview, NY), pp. 153–219 and 269–309.
  12. [12]Ishihara, T., Zhang, B., Higuchi, M., Yoshiyama, Y., Trojanowski, J. Q. & Lee, V. M. Y. (2001) Am. J. Pathol. 158, 555–562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. [13]Smith, C. M. & Swash, M. (1978) Ann. Neurol. 3, 471–473. [DOI] [PubMed] [Google Scholar]
  14. [14]Lee, V. M. Y., Balin, B. J., Otvos, L. & Trojanowski, J. Q. (1991) Science 251, 675–678. [DOI] [PubMed] [Google Scholar]
  15. [15]Barghorn, S., Zheng-Fischhofer, Q., Ackmann, M., Biernat, J., von Bergen, M., Mandelkow, E.-M. & Mandelkow, E. (2000) Biochemistry 39, 11714–11721. [DOI] [PubMed] [Google Scholar]
  16. [16]Gamblin, T. C., King, M. E., Kuret, J., Berry, R. W. & Binder, L. I. (2000) Biochemistry 39, 14203–14210. [DOI] [PubMed] [Google Scholar]
  17. [17]Lewis, J. A., Wu, C. H., Levine, J. H. & Berg, H. (1980) Neuroscience 5, 967–989. [DOI] [PubMed] [Google Scholar]
  18. [18]Thomas, J. H. (1990) Genetics 124, 855–872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. [19]McIntire, S. L., Garriga, G., White, J., Jacobson, D. & Horvitz, H. R. (1992) Neuron 8, 307–322. [DOI] [PubMed] [Google Scholar]
  20. [20]Nonet, M. L., Grundahl, K., Meyer, B. J. & Rand, J. B. (1993) Cell 73, 1291–1305. [DOI] [PubMed] [Google Scholar]
  21. [21]Avery, L., Bargmann, C. I. & Horvitz, H. R. (1993) Genetics 134, 455–464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. [22]Nguyen, M., Alfonso, A., Johnson, C. D. & Rand, J. B. (1995) Genetics 140, 527–535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. [23]Jin, Y., Jorgensen, E., Hartwieg, E. & Horvitz, H. R. (1999) J. Neurosci. 19, 539–548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. [24]Hall, D. H., Gu, G., Garcia-Anoveros, J., Gong, L., Chalfie, M. & Driscoll, M. (1997) J. Neurosci. 17, 1033–1045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. [25]Wittmann, C. W., Wszolek, M. F., Shulman, J. M., Salvaterra, P. M., Lewis, J., Hutton, M. & Feany, M. B. (2001) Science 293, 711–714. [DOI] [PubMed] [Google Scholar]
  26. [26]Spittaels, K., Van den Haute, C., Van Dorpe, J., Bruynseels, K., Vandezande, K., Laenen, I., Geerts, H., Mercken, M., Sciot, R., Van Lommel, A., et al. (1999) Am. J. Pathol. 155, 2153–2165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. [27]Lewis, J., McGowan, E., Rockwood, J., Melrose, H., Nacharaju, P., Van Slegtenhorst, M., Gwinn-Hardy, K., Murphy, M. P., Baker, M., et al. (2000) Nat. Genet. 25, 402–405. [DOI] [PubMed] [Google Scholar]
  28. [28]Spillantini, M. G., Goedert, M., Crowther, R. A., Murrell, J. R., Farlow, M. R. & Ghetti, B. (1997) Proc. Natl. Acad. Sci. USA 94, 4113–4118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. [29]D'Souza, I., Poorkaj, P., Hong, M., Nochlin, D., Lee, V. M. Y., Bird, T. D. & Schellenberg, G. D. (1999) Proc. Natl. Acad. Sci. USA 96, 5598–5603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. [30]Jackson, G. R., Wiedau-Pazos, M., Sang, T. K., Wagle, N., Brown, C. A., Massachi, S. & Geschwind, D. H. (2002) Neuron 34, 509–519. [DOI] [PubMed] [Google Scholar]
  31. [31]Spittaels, K., Van den Haute, C., Van Dorpe, J., Geerts, H., Mercken, M., Bruynseels, K., Lasrado, R., Vandezande, K., Laenen, I., Boon, T., et al. (2000) J. Biol. Chem. 275, 41340–41349. [DOI] [PubMed] [Google Scholar]
  32. [32]Brownlees, J., Irving, N. G., Brion, J. P., Gibb, B. J. M., Wagner, U., Woodgett, J. & Miller, C. C. J. (1997) NeuroReport 8, 3251–3255. [DOI] [PubMed] [Google Scholar]
  33. [33]Lucas, J. L., Hernandez, F., Gomezramos, P., Moran, M. A., Hen, R. & Avila, J. (2001) EMBO J. 20, 27–39. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. [34]Stamer, K., Vogel, R., Thies, E., Mandelkow, E. & Mandelkow, E. M. (2002) J. Cell Biol. 156, 1051–1063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. [35]Higuchi, M., Ishihara, T., Zhang, B., Hong, M., Andreadis, A., Trojanowski, J. Q. & Lee, V. M. Y. (2002) Neuron 35, 433–446. [DOI] [PubMed] [Google Scholar]
  36. [36]Daniels, S. A., Ailion, M., Thomas, J. H. & Sengupta, P. (2000) Genetics 156, 123–141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. [37]Crittenden, S. L. & Kimble, J. (1999) Methods Mol. Biol. 122, 141–151. [DOI] [PubMed] [Google Scholar]

Cited by

Sorted by citations

Authors
Kraemer, B. C., Zhang, B., Leverenz, J. B., Thomas, J. H., Trojanowski, J. Q., & Schellenberg, G. D.
Affiliations
University of Washington (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2003-07-18
Volume
100
Issue
17
Pages
9980-9985
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1533448100
PMC
PMC187908
OpenAlex
W2103147849
Cited by
379
References
4
Citations by year
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FWCI
8.64
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Veterans Affairs
  • Alzheimer's Association
  • Boehringer Ingelheim Japan
  • National Institutes of Health
  • National Institute on Aging (AG 17583)
  • National Institute of General Medical Sciences (GM-48700, R01GM048700)
  • National Institute of Child Health and Human Development
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
tauopathy, FTDP-17, tau phosphorylation, tau aggregation, neurodegeneration, neurotransmission, axonal degeneration, Caenorhabditis elegans model, P301L mutation, cholinergic inhibition, Alzheimer's disease, transgene expression
MeSH terms
Animals, Axons, Behavior, Animal, Disease Models, Animal, Humans, Immunohistochemistry, Microtubule-Associated Proteins, Mutation, Nerve Degeneration, Synaptic Transmission, Phosphorylation, Recombinant Proteins, Microscopy, Immunoelectron, tau Proteins, Caenorhabditis elegans, Tauopathies, Animals, Genetically Modified

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