Skip to main content
SpringerLink
Log in

Tau, Tangles and Tauopathies: Insights from Drosophila Disease Models

  • Chapter
  • First Online:
Insights into Human Neurodegeneration: Lessons Learnt from Drosophila

Abstract

Tauopathies, such as Alzheimer’s disease, Parkinson’s disease, Pick’s disease, etc., represent a group of neurodegenerative disorders which involve a microtubule-associated protein and tau-mediated pathogenesis and also exhibit tau inclusions in neurons or glia as their shared defining denominator. The tau protein, due to mutations or abnormal hyperphosphorylation, undergoes changes leading to the formation of aggregates in the form of paired helical filaments (PHFs) and subsequently neurofibrillary tangles (NFTs). A positive correlation between NFTs and neurodegeneration was noted, and such neurotoxic NFTs have been considered as a key factor in tau pathology. Due to limitations associated with human genetics, human tauopathies have been modelled in various organisms including Drosophila to examine the in-depths of the disease aetiology. Interestingly, brain-specific expression of the human tau-transgene in Drosophila recapitulates several pathological markers and key phenotypes. This chapter provides an overview of the molecular aspects of tau pathology and discusses the recent advances in dissecting the underlying molecular pathomechanisms using fly models.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abraha, A., Ghoshal, N., Gamblin, T. C., Cryns, V., Berry, R. W., et al. (2000). C-terminal inhibition of tau assembly in vitro and in Alzheimer’s disease. Journal of Cell Science, 113, 3737–3745.

    CAS  PubMed  Google Scholar 

  • Adams, M. D., Celniker, S. E., Holt, R. A., Evans, C. A., Gocayne, J. D., et al. (2000). The genome sequence of Drosophila melanogaster. Science, 287, 2185–2195.

    Article  PubMed  Google Scholar 

  • Alonso, A. D., Zaidi, T., Grundke-Iqbal, I., & Iqbal, K. (1994). Role of abnormally phosphorylated tau in the breakdown of microtubules in Alzheimer disease. Proceedings of the National Academy of Sciences, 91, 5562–5566.

    Article  CAS  Google Scholar 

  • Alonso, A. C., Grundke-Iqbal, I., & Iqbal, K. (1996). Alzheimer’s disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules. Nature Medicine, 2, 783–787.

    Article  CAS  PubMed  Google Scholar 

  • Alonso, A., Zaidi, T., Novak, M., Grundke-Iqbal, I., & Iqbal, K. (2001). Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments. Proceedings of the National Academy of Sciences, 98, 6923–6928.

    Article  CAS  Google Scholar 

  • Altman, J., & Sudarshan, K. (1975). Postnatal development of locomotion in the laboratory rat. Animal Behaviour, 23, 896–920.

    Article  CAS  PubMed  Google Scholar 

  • Ambegaokar, S. S., & Jackson, G. (2011). Double vision: Pigment genes do more than just color. Fly, 5, 206–209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Amos, L. A. (2004). Microtubule structure and its stabilization. Organic and Biomolecular Chemistry, 2, 2153–2160.

    Article  CAS  PubMed  Google Scholar 

  • Andreadis, A., Brown, W. M., & Kosik, K. S. (1992). Structure and novel exons of the human tau gene. The Biochemist, 31, 10626–10633.

    Article  CAS  Google Scholar 

  • Andreadis, A., Broderick, J. A., & Kosik, K. S. (1995). Relative exon affinities and suboptimal splice site signals lead to non-equivalence of two cassette exons. Nucleic Acids Research, 23, 3585–3593.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arikan, M. C., Memmott, J., Broderick, J. A., Lafyatis, R., Screaton, G., et al. (2002). Modulation of the membrane-binding projection domain of tau protein: Splicing regulation of exon 3. Brain Research. Molecular Brain Research, 101, 109–121.

    Article  CAS  PubMed  Google Scholar 

  • Augustinack, J. C., Schneider, A., Mandelkow, E. M., & Hyman, B. T. (2002). Specific tau phosphorylation sites correlate with severity of neuronal cytopathology in Alzheimer’s disease. Acta Neuropathologica, 103, 26–35.

    Article  CAS  PubMed  Google Scholar 

  • Avila, J. (2006). Tau phosphorylation and aggregation in Alzheimer’s disease pathology. FEBS Letters, 580, 2922–2927.

    Article  CAS  PubMed  Google Scholar 

  • Avila, J., Santa-Maria, I., Perez, M., Hernandez, F., & Moreno, F. (2006). Tau phosphorylation, aggregation, and cell toxicity. Journal of Biomedicine and Biotechnology, 2006(3), 1–5.

    Article  Google Scholar 

  • Bakota, L., & Brandt, R. (2016). Tau biology and tau-directed therapies for Alzheimer’s disease. Drugs, 76, 301–313.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barghorn, S., & Mandelkow, E. (2002). Towards a unified scheme for the aggregation of tau into Alzheimer Paired Helical Filaments. The Biochemist, 41, 14885–14896.

    Article  CAS  Google Scholar 

  • Barghorn, S., Zheng-Fischhofer, Q., Ackmann, M., Biernat, J., Von Bergen, M., et al. (2000). Structure, microtubule interactions, and paired helical filament aggregation by tau mutants of frontotemporal dementias. The Biochemist, 39, 11714–11721.

    Article  CAS  Google Scholar 

  • Biernat, J., Gustke, N., Drewes, G., Mandelkow, E. M., & Mandelkow, E. (1993). Phosphorylation of Ser262 strongly reduces binding of tau to microtubules: Distinction between PHF-like immunoreactivity and microtubule binding. Neuron, 11, 153–163.

    Article  CAS  PubMed  Google Scholar 

  • Binder, L. I., Guillozet-Bongaarts, A. L., Garcia-Sierra, F., & Berry, R. W. (2004). Tau, tangles, and Alzheimer’s disease. Biochim Biophys Acta, 1739, 216–223.

    Google Scholar 

  • Blard, O., Feuillette, S., Bou, J., Chaumette, B., Frébourg, T., et al. (2007). Cytoskeleton proteins are modulators of mutant tau-induced neurodegeneration in Drosophila. Human Molecular Genetics, 16, 555–566.

    Article  CAS  PubMed  Google Scholar 

  • Boyne, L. J., Tessler, A., Murray, M., & Fischer, I. (1995). Distribution of Big tau in the central nervous system of the adult and developing rat. The Journal of Comparative Neurology, 358, 279–293.

    Article  CAS  PubMed  Google Scholar 

  • Braak, H., & Braak, E. (1991). Neuropathological staging of Alzheimer-related changes. Acta Neuropthologica, 82, 239–259.

    Article  CAS  Google Scholar 

  • Braak, E., Braak, H., & Mandelkow, E. M. (1994). A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads. Acta Neuropathologica, 87, 554–567.

    Article  CAS  PubMed  Google Scholar 

  • Bramblett, G. T., Trojanowski, J. Q., & Lee, V. M.-Y. (1992). Regions with abundant neurofibrillary pathology in human brain exhibit a selective reduction in levels of binding-compentent Ù-isoforms (A68 proteins). Laboratory Investigation, 66, 212–222.

    CAS  PubMed  Google Scholar 

  • Bramblett, G. T., Goedert, M., Jakes, R., Merrick, S. E., Trojanowski, J. Q., et al. (1993). Abnormal tau phosphorylation at Ser396 in Alzheimer’s disease recapitulates development and contributes to reduced microtubule binding. Neuron, 10, 1089–1099.

    Article  CAS  PubMed  Google Scholar 

  • Brandt, R., & Lee, G. (1993). Functional organization of microtubule-associated protein tau. Identification of regions which affect microtubule growth, nucleation, and bundle formation in vitro. The Journal of Biological Chemistry, 268, 3414–3419.

    CAS  PubMed  Google Scholar 

  • Brion, J. P. (1998). Neurofibrillary Tangles and Alzheimer’s Disease. European Neurology, 40, 130–140.

    Article  CAS  PubMed  Google Scholar 

  • Brion, J. P., Smith, C., Couck, A. M., Gallo, J. M., & Anderton, B. H. (1993). Developmental changes in tau phosphorylation: Fetal tau is transiently phosphorylated in a manner similar to paired helical filament-tau characteristic of Alzheimer’s disease. Journal of Neurochemistry, 61, 2071–2080.

    Article  CAS  PubMed  Google Scholar 

  • Buée, L., Bussière, T., Buée-Scherrer, V., Delacourte, A., & Hof, P. R. (2000). Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Research Reviews, 33, 95–130.

    Article  PubMed  Google Scholar 

  • Chang, H. Y., Sang, T. K., & Chiang, A. S. (2018). Untangling the tauopathy for Alzheimer’s disease and parkinsonism. Journal of Biomedical Science, 25, 54.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chanu, S. I., & Sarkar, S. (2017). Targeted downregulation of dMyc restricts neurofibrillary tangles mediated pathogenesis of human neuronal tauopathies in Drosophila. Biochim Biophys Acta, 1863, 2111–2119.

    Google Scholar 

  • Chapin, S. J., & Bulinski, J. C. (1991). Non-neuronal 210 × 10(3) Mr microtubule-associated protein (MAP4) contains a domain homologous to the microtubule-binding domains of neuronal MAP2 and tau. Journal of Cell Science, 98, 27–36.

    CAS  PubMed  Google Scholar 

  • Chen, J., Kanai, Y., Cowan, N. J., & Hirokawa, N. (1992). Projection domains of MAP2 and tau determine spacings between microtubules in dendrites and axons. Nature, 360, 674–677.

    Article  CAS  PubMed  Google Scholar 

  • Chin, A. F., Toptygin, D., Elam, W. A., Schrank, T. P., & Hilser, V. J. (2016). Phosphorylation increases persistence length and end-to-end distance of a segment of tau protein. Biophysical Journal, 110, 362–371.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cleveland, D. W., Hwo, S. Y., & Kirschner, M. W. (1977a). Purification of tau, a microtubule-associated protein that induces assembly of microtubules from purified tubulin. Journal of Molecular Biology, 116, 207–225.

    Article  CAS  PubMed  Google Scholar 

  • Cleveland, D. W., Hwo, S. Y., & Kirschner, M. W. (1977b). Physical and chemical properties of purified tau factor and the role of tau in microtubule assembly. Journal of Molecular Biology, 116, 227–247.

    Article  CAS  PubMed  Google Scholar 

  • Cohen, T. J., Guo, J. L., Hurtado, D. E., Kwong, L. K., Mills, I. P., et al. (2011). The acetylation of tau inhibits its function and promotes pathological tau aggregation. Nature Communications, 2, 252.

    Article  PubMed  Google Scholar 

  • Cohen, T. J., Friedmann, D., Hwang, A. W., Marmorstein, R., & Lee, V. M. Y. (2013). The microtubule-associated tau protein has intrinsic acetyltransferase activity. Nature Structural & Molecular Biology, 20, 756–762.

    Article  CAS  Google Scholar 

  • Cohen, T. J., Constance, B. H., Hwang, A. W., James, M., & Yuan, C. X. (2016). Intrinsic Tau acetylation is coupled to auto-proteolytic Tau fragmentation. PLoS One, 11, e0158470.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Colodner, K. J., & Feany, M. B. (2010). Glial fibrillary tangles and JAK/STAT-mediated glial and neuronal cell death in a Drosophila model of glial tauopathy. The Journal of Neuroscience, 30, 16102–16113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cook, C., Stankowski, J. N., Carlomagno, Y., Stetler, C., & Petrucelli, L. (2014a). Acetylation: A new key to unlock tau’s role in neurodegeneration. Alzheimer’s Research & Therapy, 6, 29.

    Article  Google Scholar 

  • Cook, C., Carlomagno, Y., Gendron, T. F., Dunmore, J., Scheffel, K., et al. (2014b). Acetylation of the KXGS motifs in tau is a critical determinant in modulation of tau aggregation and clearance. Human Molecular Genetics, 23, 104–116.

    Article  CAS  PubMed  Google Scholar 

  • Correas, I., Padilla, R., & Avila, J. (1990). The tubulin-binding sequence of brain microtubule-associated proteins, tau and MAP-2, is also involved in actin binding. The Biochemical Journal, 269, 61–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Couchie, D., Mavilia, C., Georgieff, I. S., Liem, R. K., Shelanski, M. L., et al. (1992). Primary structure of high molecular weight tau present in the peripheral nervous system. Proceedings of the National Academy of Sciences, 89, 4378–4381.

    Article  CAS  Google Scholar 

  • Crespo-Biel, N., Theunis, C., Borghgraef, P., Lechat, B., Devijver, H., et al. (2014). Phosphorylation of protein tau by GSK3β prolongs survival of bigenic tau.P301L×GSK3β mice by delaying brainstem tauopathy. Neurobiology of Disease, 67, 119–132.

    Article  CAS  PubMed  Google Scholar 

  • Crowther, R. A. (1991). Straight and paired helical filaments in Alzheimer disease have a common structural unit. Proceedings of the National Academy of Sciences, 88, 2288–2292.

    Article  CAS  Google Scholar 

  • Davies, C., & Spires-Jones, T. L. (2018). Complementing Tau: new data show that the complement system is involved in degeneration in tauopathies. Neuron, 100, 1267–1269.

    Article  CAS  PubMed  Google Scholar 

  • Dehmelt, L., & Halpain, S. (2005). The MAP2/tau family of microtubule-associated proteins. Genome Biology, 6, 204.

    Article  PubMed  Google Scholar 

  • Demaegd, K., Schymkowitz, J., & Rousseau, F. (2018). Transcellular spreading of tau in tauopathies. European Journal of Chemical Biology, 19, 2424–2432.

    CAS  PubMed  Google Scholar 

  • Dickey, C. A., Kamal, A., Lundgren, K., Klosak, N., Bailey, R. M., et al. (2007). The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins. The Journal of Clinical Investigation, 117, 648–658.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ding, H., Dolan, P. J., & Johnson, G. V. (2008). Histone deacetylase 6 interacts with the microtubule-associated protein tau. Journal of Neurochemistry, 106, 2119–2130.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duyckaerts, C., Brion, J. P., Hauw, J. J., & Flament-Durand, J. (1987). Comparison of immunocytochemistry with a specific antibody and Bodian’s protargol method. Quantitative assessment of the density of neurofibrillary tangles and senile plaques in senile dementia of the Alzheimer type. Acta Neuropathol (Berl), 73, 167–170.

    Article  CAS  Google Scholar 

  • Duyckaerts, C., Delaère, P., Hauw, J. J., Abbamondi-Pinto, A. L., Sorbi, S., et al. (1990). Rating of lesions in senile dementia of the Alzheimer type: Concordance between laboratories. A European multicenter study under the auspices of Eurage. Journal of the Neurological Sciences, 97, 295–323.

    Article  CAS  PubMed  Google Scholar 

  • Elie, A., Prezel, E., Guerin, C., Denarier, E., Ramirez-Rios, S., et al. (2015). Tau co-organizes dynamic microtubule and actin networks. Scientific Reports, 5, 9964.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Esteves, A. R., Palma, A. M., Gomes, R., Santos, D., Silva, D. F., et al. (2018). Acetylation as a major determinant to microtubule-dependent autophagy: Relevance to Alzheimer’s and Parkinson disease pathology. Biochimica et Biophysica Acta, Molecular Basis of Disease. pii: S0925-4439(18)30475-7. https://doi.org/10.1016/j.bbadis.2018.11.014.

    Article  CAS  Google Scholar 

  • Felgner, H., Frank, R., Biernat, J., Mandelkow, E. M., Mandelkow, E., et al. (1997). Domains of neuronal microtubule-associated proteins and flexural rigidity of microtubules. The Journal of Cell Biology, 138, 1067–1075.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferrer, I., Gomez-Isla, T., Puig, B., Freixes, M., Ribé, E., et al. (2005). Current advances on different kinases involved in tau phosphorylation, and implications in Alzheimer’s disease and tauopathies. Current Alzheimer Research, 2, 3–18.

    Article  CAS  PubMed  Google Scholar 

  • Ferrer, I., López-González, I., Carmona, M., Arregui, L., Dalfó, E., et al. (2014). Glial and neuronal tau pathology in tauopathies: Characterization of disease-specific phenotypes and tau pathology progression. Journal of Neuropathology and Experimental Neurology, 73, 81–97.

    Article  CAS  PubMed  Google Scholar 

  • Frappier, T. F., Georgieff, I. S., Brown, K., & Shelanski, M. L. (1994). Tau regulation of microtubule–microtubule spacing and bundling. Journal of Neurochemistry, 63, 2288–2294.

    Article  CAS  PubMed  Google Scholar 

  • Friedhoff, P., Schneider, A., Mandelkow, E. M., & Mandelkow, E. (1998). Rapid assembly of Alzheimer-like paired helical filaments from microtubule-associated protein tau monitored by fluorescence in solution. The Biochemist, 37, 10223–10230.

    Article  CAS  Google Scholar 

  • Frost, B., Hemberg, M., Lewis, J., & Feany, M. B. (2014). Tau promotes neurodegeneration through global chromatin relaxation. Nature Neuroscience, 17, 357–366.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fulga, T. A., Elson-Schwab, I., Khurana, V., Steinhilb, M. L., Spires, T. L., et al. (2007). Abnormal bundling and accumulation of F-actin mediates tau-induced neuronal degeneration in vivo. Nature Cell Biology, 9, 139–148.

    Article  CAS  PubMed  Google Scholar 

  • Gamblin, T. C., King, M. E., Dawson, H., Vitek, M. P., Kuret, J., et al. (2000a). In vitro polymerization of tau protein monitored by laser light scattering: Method and application to the study of FTDP-17 mutants. Biochemistry, 39, 6136–6144.

    Article  CAS  PubMed  Google Scholar 

  • Gamblin, T. C., King, M. E., Kuret, J., Berry, R. W., & Binder, L. I. (2000b). Oxidative regulation of fatty acid-induced tau polymerization. The Biochemist, 39, 14203–14210.

    Article  CAS  Google Scholar 

  • Gamblin, T. C., Berry, R. W., & Binder, L. I. (2003a). Tau polymerization: Role of the amino terminus. The Biochemist, 42, 2252–2257.

    Article  CAS  Google Scholar 

  • Gamblin, T. C., Chen, F., Abraha, A., Miller, R., Fu, Y., et al. (2003b). Caspase cleavage of tau: Linking amyloid and neurofibrillary tangles in Alzheimer’s Disease. Proceedings of the National Academy of Sciences of the United States of America, 100, 10032–10037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garcia-Sierra, F., Ghisahl, N., Quinn, B., Berry, R., & Binder, L. I. (2003). Conformational changes and truncation of tau protein during tangle evolution in Alzheimer’s disease. Journal of Alzheimer’s Disease, 5, 65–77.

    Article  CAS  PubMed  Google Scholar 

  • Ghoshal, N., García-Sierra, F., Fu, Y., Beckett, L. A., Mufson, E. J., et al. (2001). Tau-66: Evidence for a novel tau conformation in Alzheimer’s disease. Journal of Neurochemistry, 77, 1372–1385.

    Article  CAS  PubMed  Google Scholar 

  • Giannetti, A. M., Lindwall, G., Chau, M. F., Radeke, M. J., Feinstein, S. C., et al. (2000). Fibers of tau fragments, but not full length tau, exhibit a cross β-structure: Implications for the formation of paired helical filaments. Protein Science, 9, 2427–2435.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gistelinck, M., Lambert, J. C., Callaerts, P., Dermaut, B., & Dourlen, P. (2012). Drosophila models of tauopathies: What have we learned? International Journal of Alzheimer’s Disease, 2012, 970980.

    PubMed  PubMed Central  Google Scholar 

  • Goedert, M., & Jakes, R. (1990). Expression of separate isoforms of human tau protein: Correlation with the tau pattern in brain and effects on tubulin polymerization. The EMBO Journal, 9, 4225–4230.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goedert, M., Spillantini, M. G., Cairns, N. J., & Crowther, R. A. (1992). Tau proteins of Alzheimer paired helical filaments: Abnormal phosphorylation of all six brain isoforms. Neuron, 8, 159–168.

    Article  CAS  PubMed  Google Scholar 

  • Goedert, M., Jakes, R., Crowther, R. A., Six, J., Lübke, U., et al. (1993). The abnormal phosphorylation of tau protein at Ser-202 in Alzheimer disease recapitulates phosphorylation during development. Proceedings of the National Academy of Sciences, 90, 5066–5070.

    Article  CAS  Google Scholar 

  • Goedert, M., Jakes, R., Spillantini, M. G., Hasegawa, M., Smith, M. J., et al. (1996). Assembly of microtubule-associated protein tau into Alzheimer-like filaments induced by sulphated glycosaminoglycans. Nature, 383, 550–553.

    Article  CAS  PubMed  Google Scholar 

  • Gorsky, M. K., Burnouf, S., Dols, J., Mandelkow, E., & Partridge, L. (2016). Acetylation mimic of lysine 280 exacerbates human Tau neurotoxicity in vivo. Scientific Reports, 6, 22685.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Götz, J., Halliday, G., & Nisbet, R. M. (2019). Molecular pathogenesis of the tauopathies. Annual Review of Pathology, 14, 239–261.

    Article  PubMed  CAS  Google Scholar 

  • Grundke-Iqbal, I., Iqbal, K., Tung, Y. C., Quinlan, M., Wisniewski, H. M., et al. (1986). Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proceedings of the National Academy of Sciences, 83, 4913–4917.

    Article  CAS  Google Scholar 

  • Guillozet-Bongaarts, A. L., Cahill, M. E., Cryns, V. L., Reynolds, M. R., Berry, R. W., et al. (2006). Pseudophosphorylation of tau at serine 422 inhibits caspase cleavage: In vitro evidence and implications for tangle formation in vivo. Journal of Neurochemistry, 97, 1005–1014.

    Article  CAS  PubMed  Google Scholar 

  • Guo, J. L., & Lee, V. M. (2011). Seeding of normal Tau by pathological Tau conformers drives pathogenesis of Alzheimer-like tangles. The Journal of Biological Chemistry, 286, 15317–15331.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo, T., Noble, W., & Hanger, D. P. (2017). Roles of tau protein in health and disease. Acta Neuropathologica, 133, 665–704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hall, G. F., & Yao, J. (2005). Modeling tauopathy: A range of complementary approaches. Biochim Biophys Acta, 1739, 224–239.

    Google Scholar 

  • Heidary, G., & Fortini, M. E. (2001). Identification and characterization of the Drosophila tau homolog. Mechanisms of Development, 108, 171–178.

    Article  CAS  PubMed  Google Scholar 

  • Hernández, F., & Avila, J. (2007). Tauopathies. Cellular and Molecular Life Sciences, 64, 2219–2233.

    Article  PubMed  CAS  Google Scholar 

  • Hirokawa, N., Shiomura, Y., & Okabe, S. (1988). Tau proteins: The molecular structure and mode of binding on microtubules. The Journal of Cell Biology, 107, 1449–1459.

    Article  CAS  PubMed  Google Scholar 

  • Hoffman, A., Taleski, G., & Sontag, E. (2017). The protein serine/threonine phosphatases PP2A, PP1 and calcineurin: A triple threat in the regulation of the neuronal cytoskeleton. Molecular and Cellular Neurosciences, 84, 119–131.

    Article  CAS  PubMed  Google Scholar 

  • Hong, M., Zhukareva, V., Vogelsberg-Ragaglia, V., Wszolek, Z., Reed, L., et al. (1998). Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17. Science, 282, 1914–1917.

    Article  CAS  PubMed  Google Scholar 

  • Hoover, B. R., Reed, M. N., Su, J., Penrod, R. D., Kotilinek, L. A., et al. (2010). Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration. Neuron, 68, 1067–1081.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hua, Q., He, R. Q., Haque, N., Qu, M. H., del Carmen, A. A., et al. (2003). Microtubule associated protein tau binds to double-stranded but not single-stranded DNA. Cellular and Molecular Life Sciences, 60, 413–421.

    Article  CAS  PubMed  Google Scholar 

  • Huang, D. Y., Goedert, M., Jakes, R., Weisgraber, K. H., Garner, C. C., et al. (1994). Isoform-specific interactions of apolipoprotein E with the microtubule associated protein MAP2c: Implications for Alzheimer’s disease. Neuroscience Letters, 182, 55–58.

    Article  CAS  PubMed  Google Scholar 

  • Ihara, Y., Nukina, N., Miura, R., & Ogawara, M. (1986). Phosphorylated tau protein is integrated into paired helical filaments in Alzheimer’s disease. Journal of Biochemistry, 99, 1807–1810.

    Article  CAS  PubMed  Google Scholar 

  • Irwin, D. J. (2016). Tauopathies as clinicopathological entities. Parkinsonism & Related Disorders, 22, S29–S33.

    Article  Google Scholar 

  • Irwin, D. J., Cohen, T. J., Grossman, M., Arnold, S. E., McCarty-Wood, E., et al. (2013). Acetylated tau neuropathology in sporadic and hereditary tauopathies. The American Journal of Pathology, 183, 344–351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ittner, L. M., Ke, Y. D., Delerue, F., Bi, M., Gladbach, A., et al. (2010). Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer’s disease mouse models. Cell, 142, 387–397.

    Article  CAS  PubMed  Google Scholar 

  • Ittner, A., Chua, S. W., Bertz, J., Volkerling, A., Van der Hoven, J., et al. (2016). Site-specific phosphorylation of tau inhibits amyloid-β toxicity in Alzheimer’s mice. Science, 354, 904–908.

    Article  CAS  PubMed  Google Scholar 

  • Jackson, G. R., Wiedau-Pazos, M., Sang, T. K., Wagle, N., Brown, C. A., et al. (2002). Human wild-type tau interacts with wingless pathway components and produces neurofibrillary pathology in Drosophila. Neuron, 34, 509–519.

    Article  CAS  PubMed  Google Scholar 

  • Janke, C., Beck, M., Stahl, T., Holzer, M., Brauer, K., et al. (1999). Phylogenetic diversity of the expression of the microtubule-associated protein tau: Implications for neurodegenerative disorders. Brain Research. Molecular Brain Research, 68, 119–128.

    Article  CAS  PubMed  Google Scholar 

  • Jeganathan, S., von Bergen, M., Mandelkow, E. M., & Mandelkow, E. (2008). The natively unfolded character of Tau and its aggregation to Alzheimer-like paired helical filaments. The Biochemist, 47, 10526–10539.

    Article  CAS  Google Scholar 

  • Jensen, P. H., Hager, H., Nielsen, M. S., Hojrup, P., Gliemann, J., et al. (1999). Alpha-synuclein binds to Tau and stimulates the protein kinase A-catalyzed tau phosphorylation of serine residues 262 and 356. The Journal of Biological Chemistry, 274, 25481–25489.

    Article  CAS  PubMed  Google Scholar 

  • Jovanov-Milošević, N., Petrović, D., Sedmak, G., Vukšić, M., Hof, P. R., et al. (2012). Human fetal tau protein isoform: Possibilities for Alzheimer’s disease treatment. The International Journal of Biochemistry and Cell Biology, 44, 1290–1294.

    Article  PubMed  CAS  Google Scholar 

  • Kadavath, H., Hofele, R. V., Biernat, J., Kumar, S., Tepper, K., et al. (2015). Tau stabilizes microtubules by binding at the interface between tubulin heterodimers. Proceedings of the National Academy of Sciences, 112, 7501–7506.

    Article  CAS  Google Scholar 

  • Kampers, T., Friedhoff, P., Biernat, J., Mandelkow, E. M., & Mandelkow, E. (1996). RNA stimulates aggregation of microtubule-associated protein tau into Alzheimer-like paired helical filaments. FEBS Letters, 399, 344–349.

    Article  CAS  PubMed  Google Scholar 

  • Kanaan, N. M., Morfini, G. A., LaPointe, N. E., Pigino, G. F., Patterson, K. R., et al. (2011). Pathogenic forms of tau inhibit kinesin-dependent axonal transport through a mechanism involving activation of axonal phosphotransferases. The Journal of Neuroscience, 31, 9858–9868.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kar, S., Fan, J., Smith, M. J., Goedert, M., & Amos, L. A. (2003). Repeat motifs of tau bind to the insides of microtubules in the absence of taxol. The EMBO Journal, 22, 70–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kidd, M. (1963). Paired helical filaments in electron microscopy of Alzheimer’s disease. Nature, 197, 192–193.

    Article  CAS  PubMed  Google Scholar 

  • Kimura, T., Sharma, G., Ishiguro, K., & Hisanaga, S. I. (2018). Phospho-tau bar code: Analysis of phosphoisotypes of tau and its application to tauopathy. Frontiers in Neuroscience, 12, 44.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kopke, E., Tung, Y. C., Shaikh, S., Alonso, A. C., Iqbal, K., et al. (1993). Microtubule-associated protein tau. Abnormal phosphorylation of a non-paired helical filament pool in Alzheimer disease. The Journal of Biological Chemistry, 268, 24374–24384.

    CAS  PubMed  Google Scholar 

  • Kosmidis, S., Grammenoudi, S., Papanikolopoulou, K., & Skoulakis, E. M. C. (2010). Differential effects of tau on the integrity and function of neurons essential for learning in Drosophila. The Journal of Neuroscience, 30, 464–477.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kovacs, G. G. (2015). Invited review: Neuropathology of tauopathies: Principles and practice. Neuropathology and Applied Neurobiology, 41, 3–23.

    Article  CAS  PubMed  Google Scholar 

  • Kuret, J., Chirita, C. N., Congdon, E. E., Kannanayakal, T., Li, G., et al. (2005). Pathways of tau fibrillization. Biochim Biophys Acta, 1739, 167–178.

    Article  CAS  Google Scholar 

  • Lamy, C., Duyckaerts, C., Delaere, P., Payan, C., Fermanian, J., et al. (1989). Comparison of seven staining methods for senile plaques and neurofibrillary tangles in a prospective series of 15 elderly patients. Neuropathology and Applied Neurobiology, 15, 563–578.

    Article  CAS  PubMed  Google Scholar 

  • Ledesma, M. D., Bonay, P., Colaco, C., & Avila, J. (1994). Analysis of microtubule-associated protein tau glycation in paired helical filaments. The Journal of Biological Chemistry, 269, 21614–21619.

    CAS  PubMed  Google Scholar 

  • Ledesma, M. D., Bonay, P., & Avila, J. (1995). Tau protein from Alzheimer’s disease patients is glycated at its tubulin-binding domain. Journal of Neurochemistry, 65, 1658–1664.

    Article  CAS  PubMed  Google Scholar 

  • Lee, G., Cowan, N., & Kirschner, M. (1988). The primary structure and heterogeneity of tau protein from mouse brain. Science, 239, 285–288.

    Article  CAS  PubMed  Google Scholar 

  • Lee, V. M., Goedert, M., & Trojanowski, J. Q. (2001). Neurodegenerative tauopathies. Annual Review of Neuroscience, 24, 1121–1159.

    Article  CAS  PubMed  Google Scholar 

  • Li, C., & Götz, J. (2017). Somatodendritic accumulation of Tau in Alzheimer’s disease is promoted by Fyn-mediated local protein translation. The EMBO Journal, 36, 3120–3138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li, K., Arikan, M. C., & Andreadis, A. (2003). Modulation of the membrane binding domain of tau protein: Splicing regulation of exon 2. Brain Research. Molecular Brain Research, 116, 94–105.

    Article  CAS  PubMed  Google Scholar 

  • Li, L., Wang, W., Welford, S., Zhang, T., Wang, X., et al. (2014). Ionizing radiation causes increased tau phosphorylation in primary neurons. Journal of Neurochemistry, 131, 86–93.

    Article  CAS  PubMed  Google Scholar 

  • Lin, C. H., Tsai, P. I., Wu, R. W., & Chien, C. T. (2010). LRRK2 G2019S mutation induces dendrite degeneration through mislocalization and phosphorylation of tau by recruiting autoactivated GSK3β. Journal of Neuroscience, 30, 13138–13149.

    Article  CAS  PubMed  Google Scholar 

  • Lindwall, G., & Cole, R. D. (1984). Phosphorylation affects the ability of tau protein to promote microtubule assembly. The Journal of Biological Chemistry, 259, 5301–5305.

    CAS  PubMed  Google Scholar 

  • Liu, F., Zaidi, T., Iqbal, K., Grundke-Iqbal, I., & Gong, C. X. (2002). Aberrant glycosylation modulates phosphorylation of tau by protein kinase A and dephosphorylation of tau by protein phosphatase 2A and 5. Neuroscience, 115, 829–837.

    Article  CAS  PubMed  Google Scholar 

  • Liu, F., Iqbal, K., Grundke-Iqbal, I., Hart, G. W., & Gong, C. X. (2004). O-GlcNAcylation regulates phosphorylation of tau: A mechanism involved in Alzheimer’s disease. Proceedings of the National Academy of Sciences of the United States of America, 101, 10804–10809.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu, F., Grundke-Iqbal, I., Iqbal, K., & Gong, C. X. (2005). Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of tau phosphorylation. The European Journal of Neuroscience, 22, 1942–1950.

    Article  PubMed  Google Scholar 

  • Lu, P. J., Wulf, G., Zhou, X. Z., Davies, P., & Lu, K. P. (1999). The prolyl isomerase Pin1 restores the function of Alzheimer-associated phosphorylated tau protein. Nature, 399, 784–788.

    Article  CAS  PubMed  Google Scholar 

  • Luo, Y., Ma, B. Y., Nussinov, R., & Wei, G. H. (2014). Structural insight into tau protein’s paradox of intrinsically disordered behavior, self-acetylation activity, and aggregation. Journal of Physical Chemistry Letters, 5, 3026–3031.

    Article  CAS  PubMed  Google Scholar 

  • Ma, X., Li, H., He, Y., & Hao, J. (2017). The emerging link between O-GlcNAcylation and neurological disorders. Cellular and Molecular Life Sciences, 74, 3667–3686.

    Article  CAS  PubMed  Google Scholar 

  • Mandelkow, E. M., & Mandelkow, E. (2012). Biochemistry and cell biology of tau protein in neurofibrillary degeneration. Cold Spring Harbor Perspectives in Medicine, 2, a006247.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mandelkow, E. M., Schweers, O., Drewes, G., Biernat, J., Gustke, N., et al. (1996). Structure, microtubule interactions, and phosphorylation of tau protein. Annals of the New York Academy of Sciences, 777, 96–106.

    Article  CAS  PubMed  Google Scholar 

  • Martin, L., Latypova, X., & Terro, F. (2011). Post-translational modifications of tau protein: Implications for Alzheimer’s disease. Neurochemistry International, 58, 458–471.

    Article  CAS  PubMed  Google Scholar 

  • Matsumoto, S. E., Motoi, Y., Ishiguro, K., Tabira, T., Kametani, F., et al. (2015). The twenty-four KDa C-terminal tau fragment increases with aging in tauopathy mice: Implications of prion-like properties. Human Molecular Genetics, 24, 6403–6416.

    Article  CAS  PubMed  Google Scholar 

  • Maurer, K., Volk, S., & Gerbaldo, H. (1997). Auguste D and Alzheimer’s disease. Lancet, 349, 1546–1549.

    Article  CAS  PubMed  Google Scholar 

  • McDermott, J. B., Aamodt, S., & Aamodt, E. (1996). ptl-1, a Caenorhabditis elegans gene whose products are homologous to the tau microtubule-associated proteins. The Biochemist, 35, 9415–9423.

    Article  CAS  Google Scholar 

  • Mietelska-Porowska, A., Wasik, U., Goras, M., Filipek, A., & Niewiadomska, G. (2014). Tau protein modifications and interactions: Their role in function and dysfunction. International Journal of Molecular Sciences, 15, 4671–4713.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Min, S. W., Cho, S. H., Zhou, Y., Schroeder, S., Haroutunian, V., et al. (2010). Acetylation of tau inhibits its degradation and contributes to tauopathy. Neuron, 67, 953–966.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Min, S. W., Chen, X., Tracy, T. E., Li, Y., Zhou, Y., et al. (2015). Critical role of acetylation in tau-mediated neurodegeneration and cognitive deficits. Nature Medicine, 21, 1154–1162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Minamide, L. S., Striegl, A. M., Boyle, J. A., Meberg, P. J., & Bamburg, J. R. (2000). Neurodegenerative stimuli induce persistent ADF/cofilin-actin rods that disrupt distal neurite function. Nature Cell Biology, 2, 628–636.

    Article  CAS  PubMed  Google Scholar 

  • Mirbaha, H., Chen, D., Morazova, O. A., Ruff, K. M., Sharma, A. M., et al. (2018). Inert and seed-competent tau monomers suggest structural origins of aggregation. eLife, 7, pii: e36584.

    Article  Google Scholar 

  • Moreno, H., Morfini, G., Buitrago, L., Ujlaki, G., Choi, S., et al. (2016). Tau pathology-mediated presynaptic dysfunction. Neuroscience, 325, 30–38.

    Article  CAS  PubMed  Google Scholar 

  • Morris, M., Maeda, S., Vossel, K., & Mucke, L. (2011). The many faces of tau. Neuron, 70, 410–426.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morris, M., Knudsen, G. M., Maeda, S., Trinidad, J. C., Ioanoviciu, A., et al. (2015). Tau post-translational modifications in wild-type and human amyloid precursor protein transgenic mice. Nature Neuroscience, 18, 1183–1189.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mukaetova-Ladinska, E. B., Harrington, C. R., Roth, M., & Wischik, C. M. (1993). Biochemical and anatomical redistribution of tau protein in Alzheimer’s disease. The American Journal of Pathology, 143, 565–578.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mukrasch, M. D., von Bergen, M., Biernat, J., Fischer, D., Griesinger, C., et al. (2007). The “jaws” of microtubule interaction. The Journal of Biological Chemistry, 282, 12230–12239.

    Article  CAS  PubMed  Google Scholar 

  • Mukrasch, M. D., Bibow, S., Korukottu, J., Jeganathan, S., Biernat, J., et al. (2009). Structural polymorphism of 441-residue Tau at single residue resolution. PLoS Biology, 7, e1000034.

    Article  PubMed Central  CAS  Google Scholar 

  • Murray, M. E., Kouri, N., Lin, W. L., Jack, C. R., Jr., Dickson, D. W., et al. (2014). Clinicopathologic assessment and imaging of tauopathies in neurodegenerative dementias. Alzheimer’s Research & Therapy, 6, 1.

    Article  Google Scholar 

  • Neve, R. L., Harris, P., Kosik, K. S., Kurnit, D. M., & Donlon, T. A. (1986). Identification of cDNA clones for the human microtubule-associated protein tau and chromosomal localization of the genes for tau and microtubule-associated protein 2. Molecular Brain Research, 1, 271–280.

    Article  CAS  Google Scholar 

  • Nunez, J., & Fischer, I. (1997). Microtubule-associated proteins (MAPs) in the peripheral nervous system during development and regeneration. Journal of Molecular Neuroscience, 8, 207–222.

    Article  CAS  PubMed  Google Scholar 

  • Orr, M. E., Sullivan, A. C., & Frost, B. (2017). A brief overview of tauopathy: Causes, consequences, and therapeutic strategies. Trends in Pharmacological Sciences, 38, 637–648.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ozansoy, M., & Başak, A. (2007). Tauopathies: A distinct class of neurodegenerative diseases. Balkan Journal of Medical Genetics: BJMG, 10, 3–14.

    Article  CAS  Google Scholar 

  • Pierre, M., & Nunez, J. (1983). Multisite phosphorylation of tau proteins from rat brain. Biochemical and Biophysical Research Communications, 115, 212–219.

    Article  CAS  PubMed  Google Scholar 

  • Qiang, L., Yu, W., Andreadis, A., Luo, M., & Baas, P. W. (2006). Tau protects microtubules in the axon from severing by katanin. The Journal of Neuroscience, 26, 3120–3129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reiter, L. T., Potocki, L., Chien, S., Gribskov, M., & Bier, E. (2001). A systematic analysis of human disease-associated gene sequences in Drosophila melanogaster. Genome Research, 11, 1114–1125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reyes, J. F., Geula, C., Vana, L., & Binder, L. I. (2012). Selective tau tyrosine nitration in non-AD tauopathies. Acta Neuropathologica, 123, 119–132.

    Article  CAS  PubMed  Google Scholar 

  • Rodríguez-Martín, T., Cuchillo-Ibáñez, I., Noble, W., Nyenya, F., Anderton, B. H., et al. (2013). Neurobiology of Aging, 34, 2146–2157.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Saha, P., & Sen, N. (2019). Tauopathy: A common mechanism for neurodegeneration and brain aging. Mechanisms of Ageing and Development, 178, 72–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sarkar, S. (2018). Neurofibrillary tangles mediated human neuronal tauopathies: Insights from fly models. Journal of Genetics, 97, 783–793.

    Article  CAS  PubMed  Google Scholar 

  • Scales, T. M., Derkinderen, P., Leung, K. Y., Byers, H. L., Ward, M. A., et al. (2001). Tyrosine phosphorylation of tau by the SRC family kinases lck and fyn. Molecular Neurodegeneration, 6, 12.

    Article  CAS  Google Scholar 

  • Schneider, A., Biernat, J., von Bergen, M., Mandelkow, E., & Mandelkow, E. M. (1999). Phosphorylation that detaches tau protein from microtubules (Ser262, Ser214) also protects it against aggregation into Alzheimer paired helical filaments. The Biochemist, 38, 3549–3558.

    Article  CAS  Google Scholar 

  • Schweers, O., Mandelkow, E. M., Biernat, J., & Mandelkow, E. (1995). Oxidation of cysteine-322 in the repeat domain of microtubule-associated protein tau controls the in vitro assembly of paired helical filaments. Proceedings of the National Academy of Sciences, 92, 8463–8467.

    Article  CAS  Google Scholar 

  • Seitz, A., Kojima, H., Oiwa, K., Mandelkow, E. M., Song, Y. H., et al. (2002). Single-molecule investigation of the interference between kinesin, tau and MAP2c. The EMBO Journal, 21, 4896–4905.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sergeant, N., Delacourte, A., & Buée, L. (2005). Tau protein as a differential biomarker of tauopathies. Biochim Biophys Acta, 1739, 179–197.

    Google Scholar 

  • Sergeant, N., Bretteville, A., Hamdane, M., Caillet-Boudin, M. L., Grognet, P., et al. (2008). Biochemistry of Tau in Alzheimer’s disease and related neurological disorders. Expert Review of Proteomics, 5, 207–224.

    Article  CAS  PubMed  Google Scholar 

  • Serrano-Pozo, A., Frosch, M. P., Masliah, E., & Hyman, B. T. (2011). Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect, 1, a006189.

    Google Scholar 

  • Shulman, J. M., & Feany, M. B. (2003). Genetic modifiers of tauopathy in Drosophila. Genetics, 165, 1233–1242.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sillen, A., Barbier, P., Landrieu, I., Lefebvre, S., Wieruszeski, J. M., et al. (2007). NMR investigation of the interaction between the neuronal protein tau and the microtubules. The Biochemist, 46, 3055–3064.

    Article  CAS  Google Scholar 

  • Simons, D. J., & Land, P. W. (1987). Early experience of tactile stimulation influences organization of somatic sensory cortex. Nature, 326, 694–697.

    Article  CAS  PubMed  Google Scholar 

  • Sivanantharajah, L., Mudher, A., & Shepherd, D. (2019). An evaluation of Drosophila as a model system for studying tauopathies such as Alzheimer’s disease. Journal of Neuroscience Methods, 319, 77–88. pii: S0165-0270(19)30007-X.

    Article  CAS  PubMed  Google Scholar 

  • Smet-Nocca, C., Broncel, M., Wieruszeski, J. M., Tokarski, C., Hanoulle, X., et al. (2011). Identification of O-GlcNAcsites within peptides of the Tau protein and their impact on phosphorylation. Molecular BioSystems, 7, 1420–1429.

    Article  CAS  PubMed  Google Scholar 

  • Smolek, T., Jadhav, S., Brezovakova, V., Cubinkova, V., Valachova, B., et al. (2018). First-in-rat study of human Alzheimer’s disease Tau propagation. Molecular Neurobiology. https://doi.org/10.1007/s12035-018-1102-0.

    Article  PubMed  CAS  Google Scholar 

  • Spillantini, M. G., & Goedert, M. (1998). Tau protein pathology in neurodegenerative diseases. Trends in Neurosciences, 21, 428–433.

    Article  CAS  PubMed  Google Scholar 

  • Su, J. H., Cummings, B. J., & Cotman, C. W. (1993). Identification and distribution of axonal dystrophic neurites in Alzheimer’s disease. Brain Research, 625, 228–237.

    Article  CAS  PubMed  Google Scholar 

  • Takashima, A., Murayama, M., Murayama, O., Kohno, T., Honda, T., et al. (1998). Presenilin 1 associates with glycogen synthase kinase-3beta and its substrate tau. Proceedings of the National Academy of Sciences, 95, 9637–9641.

    Article  CAS  Google Scholar 

  • Tapia-Rojas, C., Cabezas-Opazo, F., Deaton, C. A., Vergara, E. H., Johnson, G. V. W., et al. (2018). It’s all about tau. Progress in Neurobiology. pii: S0301–0082(17)30237-X. https://doi.org/10.1016/j.pneurobio.2018.12.005.

    Article  CAS  PubMed  Google Scholar 

  • Tracy, T. E., Sohn, P. D., Minami, S. S., Wang, C., Min, S. W., et al. (2015). Acetylated tau obstructs KIBRA-mediated signaling in synaptic plasticity and promotes tauopathy-related memory loss. Neuron, 90, 245–260.

    Article  CAS  Google Scholar 

  • Tremblay, M. A., Acker, C. M., & Davies, P. (2010). Tau phosphorylated at tyrosine 394 is found in Alzheimer’s disease tangles and can be a product of the Abl-related kinase, Arg. Journal of Alzheimer’s Disease, 19, 721–733.

    Article  CAS  PubMed  Google Scholar 

  • Trotter, M. B., Stephens, T. D., McGrath, J. P., & Steinhilb, M. L. (2017). The Drosophila model system to study tau action. Methods in Cell Biology, 141, 259–286.

    Article  PubMed  Google Scholar 

  • Vershinin, M., Carter, B. C., Razafsky, D. S., King, S. J., & Gross, S. P. (2007). Multiple-motor based transport and its regulation by Tau. Proceedings of the National Academy of Sciences, 104, 87–92.

    Article  CAS  Google Scholar 

  • von Bergen, M., Friedhoff, P., Biernat, J., Heberle, J., Mandelkow, E. M., et al. (2000). Assembly of tau protein into Alzheimer paired helical filaments depends on a local sequence motif ((306)VQIVYK(311)) forming beta structure. Proceedings of the National Academy of Sciences, 97, 5129–5134.

    Article  CAS  Google Scholar 

  • von Bergen, M., Barghorn, S., Li, L., Marx, A., Biernat, J., et al. (2001). Mutations of tau protein in frontotemporal dementia promote aggregation of paired helical filaments by enhancing local beta-structure. The Journal of Biological Chemistry, 276, 48165–48174.

    Article  Google Scholar 

  • Wang, Y., & Mandelkow, E. (2016). Tau in physiology and pathology. Nature Reviews. Neuroscience, 17, 5–21.

    Article  PubMed  CAS  Google Scholar 

  • Wang, J. Z., Grundke-Iqbal, I., & Iqbal, K. (1996). Glycosylation of microtubule-associated protein tau: An abnormal posttranslational modification in Alzheimer’s disease. Nature Medicine, 2, 871–875.

    Article  CAS  PubMed  Google Scholar 

  • Wang, J., Gao, Q. S., Wang, Y., Lafyatis, R., Stamm, S., et al. (2004). Tau exon10, whose missplicing causes frontotemporal dementia, is regulated by an intricate interplay of cis elements and trans factors. Journal of Neurochemistry, 88, 1078–1090.

    Article  CAS  PubMed  Google Scholar 

  • Watanabe, A., Hong, W. K., Dohmae, N., Takio, K., Morishima-Kawashima, M., et al. (2004). Molecular aging of tau: Disulfide-independent aggregation and non-enzymatic degradation in vitro and in vivo. Journal of Neurochemistry, 90, 1302–1311.

    Article  CAS  PubMed  Google Scholar 

  • Wei, Y., Qu, M. H., Wang, X. S., Chen, L., Wang, D. L., et al. (2008). Binding to the minor groove of the double-strand, tau protein prevents DNA from damage by peroxidation. PLoS One, 3, e2600.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Weingarten, M. D., Lockwood, A. H., Hwo, S. Y., & Kirschner, M. W. (1975). A protein factor essential for microtubule assembly. Proceedings of the National Academy of Sciences, 72, 1858–1862.

    Article  CAS  Google Scholar 

  • Weingarten, M. D., Lockwood, A. H., Hwo, S. Y., & Kirschner, M. W. (1976). A protein factor essential for microtubule assembly. Proceedings of the National Academy of Sciences, 72, 1858–1862.

    Article  Google Scholar 

  • Weismiller, H. A., Murphy, R., Wei, G., Ma, B., Nussinov, R., et al. (2018). Structural disorder in four-repeat Tau fibrils reveals a new mechanism for barriers to cross-seeding of Tau isoforms. The Journal of Biological Chemistry, 293, 17336–17348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wheeler, J. M., Guthrie, C. R., & Kraemer, B. C. (2012). Potential neuroprotective strategies against tauopathy. Biochemical Society Transactions, 40, 656–660.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wille, H., Drewes, G., Biernat, J., Mandelkow, E. M., & Mandelkow, E. (1992). Alzheimer-like paired helical filaments and antiparallel dimers formed from microtubule-associated protein tau in vitro. The Journal of Cell Biology, 118, 573–584.

    Article  CAS  PubMed  Google Scholar 

  • Williams, D. R. (2006). Tauopathies: Classification and clinical update on neurodegenerative diseases associated with microtubule-associated protein tau. Internal Medicine Journal, 36, 652–660.

    Article  CAS  PubMed  Google Scholar 

  • Williams, D. W., Tyrer, M., & Shepherd, D. (2000). Tau and tau reporters disrupt central projections of sensory neurons in Drosophila. The Journal of Comparative Neurology, 428, 630–640.

    Article  CAS  PubMed  Google Scholar 

  • Wischik, C. M. (1989). Cell biology of Alzheimer tangle. Current Opinion in Cell Biology, 1, 115–122.

    Article  CAS  PubMed  Google Scholar 

  • Wisniewski, H. M., Narang, H. K., & Terry, R. D. (1976). Neurofibrillary tangles of paired helical filaments. Journal of the Neurological Sciences, 27, 173–181.

    Article  CAS  PubMed  Google Scholar 

  • Wittmann, C. W., Wszolek, M. F., Shulman, J. M., Salvaterra, P. M., Lewis, J., et al. (2001). Tauopathy in Drosophila: Neurodegeneration without neurofibrillary tangles. Science, 293, 711–714.

    Article  CAS  PubMed  Google Scholar 

  • Woody, R. W., Clark, D. C., Roberts, G. C., Martin, S. R., & Bayley, P. M. (1983). Molecular flexibility in microtubule proteins: Proton nuclear magnetic resonance characterization. The Biochemist, 22, 2186–2192.

    Article  CAS  Google Scholar 

  • Wu, T. H., Lu, Y. N., Chuang, C. L., Wu, C. L., Chiang, A. S., et al. (2013). Loss of vesicular dopamine release precedes tauopathy in degenerative dopaminergic neurons in a Drosophila model expressing human tau. Acta Neuropathologica, 125, 711–725.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang, X. J., & Seto, E. (2008). Lysine acetylation: Codified crosstalk with other posttranslational modifications. Molecular Cell, 31, 449–461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuzwa, S. A., Cheung, A. H., Okon, M., McIntosh, L. P., & Vocadlo, D. J. (2014). O-GlcNAc modification of tau directly inhibits its aggregation without perturbing the conformational properties of tau monomers. Journal of Molecular Biology, 426, 1736–1752.

    Article  CAS  PubMed  Google Scholar 

  • Zhou, L., McInnes, J., Wierda, K., Holt, M., Herrmann, A. G., et al. (2017). Tau association with synaptic vesicles causes presynaptic dysfunction. Nature Communications, 8, 15295.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

Research works on neurodegenerative disorders in the lab is supported by the grants from Department of Biotechnology (DBT), Government of India, New Delhi. We also thank Delhi University for financial support under DU/DST-PURSE scheme. We are grateful to Ms Nabanita Sarkar for the technical help.

Author information

Authors and Affiliations

  1. Department of Genetics, University of Delhi South Campus, Benito Juarez Road, New Delhi, India

    Nisha,  Pragati, Shweta Tandon,  Aqsa, Prerna Aggarwal & Surajit Sarkar

Authors
  1. Nisha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pragati
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shweta Tandon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aqsa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Prerna Aggarwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Surajit Sarkar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Surajit Sarkar .

Editor information

Editors and Affiliations

  1. Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, Uttar Pradesh, India

    Mousumi Mutsuddi

  2. Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, Uttar Pradesh, India

    Ashim Mukherjee

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Nisha, Pragati, Tandon, S., Aqsa, Aggarwal, P., Sarkar, S. (2019). Tau, Tangles and Tauopathies: Insights from Drosophila Disease Models. In: Mutsuddi, M., Mukherjee, A. (eds) Insights into Human Neurodegeneration: Lessons Learnt from Drosophila. Springer, Singapore. https://doi.org/10.1007/978-981-13-2218-1_8

Download citation

Publish with us

Policies and ethics

Search

Navigation