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Neurofibrillary tangles mediated human neuronal tauopathies: insights from fly models

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Abstract

Tauopathies represent a group of neurodegenerative disorder which are characterized by the presence of tau positive specialized argyrophilic and insoluble intraneuronal and glial fibrillar lesions known as neurofibrillary tangles (NFTs). Tau is a neuron specific microtubule binding protein which is required for the integrity and functioning of neuronal cells, and hyperphosphorylation of tau and its subsequent aggregation and paired helical filaments (PHFs) and NFTs has emerged as one of the major pathogenic mechanisms of tauopathies in human and mammalian model systems. Modeling of human tauopathies in Drosophila results in manifestation of associated phenotypes, and a recent study has demonstrated that similar to human and mammalian models, accumulation of insoluble tau aggregates in the form of typical neurotoxic NFTs triggers the pathogenesis of tauopathies in fly models. In view of the availability of remarkable genetic tools, Drosophila tau models could be extremely useful for in-depth analysis of the role of NFTs in neurodegeneration and tau aetiology, and also for the screening of novel gene(s) and molecule(s) which suppress the toxicity of tau aggregates.

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References

  • Aamodt E. J. and Williams R. C. Jr. 1984 Microtubule-associated proteins connect microtubules and neurofilaments in vitro. Biochemistry 23, 6023–6031.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Alonso A., Zaidi T., Novak M., Grundke-Iqbal I. and Iqbal K. 2001 Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments. Proc. Natl. Acad. Sci. USA 98, 6923–6928.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Alzheimer A. 1907 Uber eine eigenartige Erkrankung der Hirnridne [about a peculiar disease of the cerebral cortex]. Allg. Z Psychiatr. 64, 4648.

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Barghorn S., Zheng-Fischhöfer Q., Ackmann M., Biernat J. and von Bergen M. et al. 2000 Structure, microtubule interactions, and paired helical filament aggregation by tau mutants of frontotemporal dementias. Biochemistry 39, 11714–11721.

    Article  PubMed  CAS  Google Scholar 

  • Biernat J., Gustke N., Drewes G., Mandelkow E. M. and 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  PubMed  CAS  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  PubMed  CAS  Google Scholar 

  • Brandt R., Léger J. and Lee G. 1995 Interaction of tau with the neural plasma membrane mediated by tau’s amino-terminal projection domain. J. Cell Biol. 131, 1327–1340.

    Article  PubMed  CAS  Google Scholar 

  • Brion J. P., Smith C., Couck A. M., Gallo J. M. and 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. J. Neurochem. 61, 2071–2080.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Chanu S. I. and Sarkar S. 2017a Targeted downregulation of dMyc suppresses pathogenesis of human neuronal tauopathies in Drosophila by limiting heterochromatin relaxation and tau hyperphosphorylation. Mol. Neurobiol. 54, 2706–2719.

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Chen S., Townsend K., Goldberg T. E., Davies P. and Conejero-Goldberg C. 2010 MAPT isoforms: differential transcriptional profiles related to 3R and 4R splice variants. J. Alzheimers Dis. 22, 1313–1329.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Conde C. and Cáceres A. 2009 Microtubule assembly, organization and dynamics in axons and dendrites. Nat. Rev. Neurosci. 10, 319–332.

    Article  PubMed  CAS  Google Scholar 

  • Congdon E. E., Kim S., Bonchak J., Songrug T. and Matzavinos A. et al. 2008 Nucleation-dependent tau filament formation: the importance of dimerization and an estimation of elementary rate constants. J. Biol. Chem. 283, 13806–13816.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cope T. E., Rittman T., Borchert R. J., Jones P. S. and Vatansever D. et al. 2018 Tau burden and the functional connectome in Alzheimer’s disease and progressive supranuclear palsy. Brain 141, 550–567.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cripps D., Thomas S. N., Jeng Y., Yang F. and Davies P. et al. 2006 Alzheimer disease-specific conformation of hyperphosphorylated paired helical filament-Tau is polyubiquitinated through Lys-48, Lys-11, and Lys-6 ubiquitin conjugation. J. Biol. Chem. 281, 10825–10838.

    Article  PubMed  CAS  Google Scholar 

  • Dehmelt L. and Halpain S. 2005 The MAP2/Tau family of microtubule-associated proteins. Genome Biol. 6, 204.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dickson D. W., Kouri N., Murray M. E. and Josephs K. A. 2011 Neuropathology of frontotemporal lobar degeneration-tau (FTLD-tau). J. Mol. Neurosci. 45, 384–389.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Feinstein S. C. and Wilson L. 2005 Inability of tau to properly regulate neuronal microtubule dynamics: a loss-of-function mechanism by which tau might mediate neuronal cell death. Biochim. Biophys. Acta. 1739, 268–279.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Frappier T. F., Georgieff I. S., Brown K. and Shelanski M. L. 1994 tau Regulation of microtubule-microtubule spacing and bundling. J. Neurochem. 63, 2288–2294.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Gistelinck M., Lambert J. C., Callaerts P., Dermaut B. and Dourlen P. 2012 Drosophila models of tauopathies: what have we learned? Int. J. Alzheimers Dis. 2012, 970980.

    PubMed  PubMed Central  Google Scholar 

  • Goedert M. and Jakes R. 1990 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Goedert M., Jakes R., Crowther R. A., Six J. and Lübke U. et al. 1993 The abnormal phosphorylation of tau protein at Ser-202 in Alzheimer disease recapitulates phosphorylation during development. Proc. Natl. Acad. Sci. USA 90, 5066–5070.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Goedert M., Ghetti B. and Spillantini M. G. 2012 Frontotemporal dementia: implications for understanding Alzheimer disease. Cold Spring Harb. Perspect. Med. 2, a006254.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Goedert M., Eisenberg D. S. and Crowther R. A. 2017 Propagation of tau aggregates and neurodegeneration. Annu. Rev. Neurosci. 40, 189–210.

    Article  PubMed  CAS  Google Scholar 

  • Götz J., Chen F., van Dorpe J. and Nitsch R. M. 2001 Formation of neurofibrillary tangles in P301 l tau transgenic mice induced by Abeta 42 fibrils. Science 293, 1491–1495.

    Article  PubMed  Google Scholar 

  • Griffith L. M. and Pollard T. D. 1978 Evidence for actin filament-microtubule interaction mediated by microtubule-associated proteins. J. Cell Biol. 78, 958–965.

    Article  PubMed  CAS  Google Scholar 

  • Guillozet-Bongaarts A. L., Cahill M. E., Cryns V. L., Reynolds M. R. and 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. J. Neurochem. 97, 1005–1014.

    Article  PubMed  CAS  Google Scholar 

  • Hardy J. and Singleton A. 2008 The HapMap: charting a course for genetic discovery in neurological diseases. Arch. Neurol. 65, 319–321.

    Article  PubMed  Google Scholar 

  • Hirokawa N., Shiomura Y. and Okabe S. 1988 Tau proteins: the molecular structure and mode of binding on microtubules. J. Cell Biol. 107, 1449–1459.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Jackson G. R., Wiedau-Pazos M., Sang T. K., Wagle N. and 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  PubMed  CAS  Google Scholar 

  • Jovanov-Milošević N., Petrović D., Sedmak G., Vukšić M. and Hof P. R. et al. 2012 Human fetal tau protein isoform: possibilities for Alzheimer’s disease treatment. Int. J. Biochem. Cell Biol. 44, 1290–1294.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Köpke E., Tung Y. C., Shaikh S., Alonso A. C. and Iqbal K. et al. 1993 Microtubule-associated protein tau. Abnormal phosphorylation of a non-paired helical filament pool in Alzheimer disease. J. Biol. Chem. 268, 24374–24384.

    PubMed  Google Scholar 

  • Kovacs G. G. 2015 Neuropathology of tauopathies: principles and practice. Neuropathol. Appl. Neurobiol. 41, 3–23.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Lee G. and Leugers C. J. 2012 Tau and tauopathies. Prog. Mol. Biol. Transl. Sci. 107, 263–293.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Lee G., Neve R. L. and Kosik K. S. 1989 The microtubule binding domain of tau protein. Neuron 2, 1615–1624.

    Article  PubMed  CAS  Google Scholar 

  • Lee V. M., Goedert M. and Trojanowski J. Q. 2001 Neurodegenerative tauopathies. Annu. Rev. Neurosci. 24, 1121–1159.

    Article  PubMed  CAS  Google Scholar 

  • Lee V. M., Kenyon T. K. and Trojanowski J. Q. 2005 Transgenic animal models of tauopathies. Biochim. Biophys. Acta. 1739, 251–259.

    Article  PubMed  CAS  Google Scholar 

  • Lewis J., McGowan E., Rockwood J., Melrose H. and Nacharaju P. et al. 2000 Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Nat. Genet. 25, 402–405.

    Article  PubMed  CAS  Google Scholar 

  • Lim S., Haque M. M., Kim D., Kim D. J. and Kim Y. K. 2014 Cell-based models to investigate tau aggregation. Comput. Struct. Biotechnol. J. 12, 7–13.

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu F., Grundke-Iqbal I., Iqbal K. and Gong C. X. 2005 Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of tau phosphorylation. Eur. J. Neurosci. 22, 1942–1950.

    Article  PubMed  Google Scholar 

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

  • Mandelkow E. M. and Mandelkow E. 2012 Biochemistry and cell biology of tau protein in neurofibrillary degeneration. Cold Spring Harb. Perspect. Med. 2, a006247.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Marsh J. L. and Thompson L. M. 2006 Drosophila in the study of neurodegenerative disease. Neuron 52, 169–178.

    Article  PubMed  CAS  Google Scholar 

  • McGurk L., Berson A. and Bonini N. M. 2015 Drosophila as an in vivo model for human neurodegenerative disease. Genetics 201, 377–402.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mershin A., Pavlopoulos E., Fitch O., Braden B. C. and Nanopoulos D. V. et al. 2004 Learning and memory deficits upon tau accumulation in Drosophila mushroom body neurons. Learn. Mem. 11, 277–287.

    Article  PubMed  PubMed Central  Google Scholar 

  • Nussbaum J. M., Schilling S., Cynis H., Silva A. and Swanson E. et al. 2012 Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-\(\upbeta \). Nature 485, 651–655.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pandey U. B. and Nichols C. D. 2011 Human disease models in Drosophila melanogaster and the role of the fly in therapeutic drug discovery. Pharmacol. Rev. 63, 411–436.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Peeraer E., Bottelbergs A., Van Kolen K., Stancu I. C. and Vasconcelos B. et al. 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.

    Article  PubMed  CAS  Google Scholar 

  • Poorkaj P., Bird T. D., Wijsman E., Nemens E. and Garruto R. M. et al. 1998 Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann. Neurol. 43, 815–825.

    Article  PubMed  CAS  Google Scholar 

  • Povova J., Ambroz P., Bar M., Pavukova V. and Sery O. et al. 2012 Epidemiological of and risk factors for Alzheimer’s disease: a review. Biomed. Pap. Med. Fac. Univ. Palacky. Olomouc. Czech. Repub. 156, 108–114.

    Article  PubMed  Google Scholar 

  • Reynolds M. R., Berry R. W. and Binder L. I. 2005 Site-specific nitration and oxidative dityrosine bridging of the tau protein by peroxynitrite: implications for Alzheimer’s disease. Biochemistry 44, 1690–1700.

    Article  PubMed  CAS  Google Scholar 

  • Scales T. M, Derkinderen P., Leung K. Y., Byers H. L. and Ward M. A. et al. 2011 Tyrosine phosphorylation of tau by the SRC family kinases lck and fyn. Mol. Neurodegener. 6, 12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Schneider A. and Mandelkow E. 2008 Tau-based treatment strategies in neurodegenerative diseases. Neurotherapeutics 5, 443–457.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Singh M. D., Raj K. and Sarkar S. 2014 Drosophila Myc, a novel modifier suppresses the poly(Q) toxicity by modulating the level of CREB binding protein and histone acetylation. Neurobiol. Dis. 63, 48–61.

    Article  PubMed  CAS  Google Scholar 

  • Smid L. M., Kepe V., Vinters H. V., Bresjanac M. and Toyokuni T. et al. 2013 Postmortem 3-D brain hemisphere cortical tau and amyloid-\(\upbeta \) pathology mapping and quantification as a validation method of neuropathology imaging. J. Alzheimers Dis. 36, 261–274.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Stork T., Engelen D., Krudewig A., Silies M. and Bainton R. J. 2008 Organization and function of the blood-brain barrier in Drosophila. J. Neurosci. 28, 587–597.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Takuma H., Arawaka S. and Mori H. 2003 Isoforms changes of tau protein during development in various species. Brain Res. Dev. Brain Res. 142, 121–127.

    Article  PubMed  CAS  Google Scholar 

  • Tanemura K., Murayama M., Akagi T., Hashikawa T. and Tominaga T. et al. 2002 Neurodegeneration with tau accumulation in a transgenic mouse expressing V337 M human tau. J. Neurosci. 22, 133–141.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Tatebayashi Y., Miyasaka T., Chui D. H., Akagi T. and Mishima K. et al. 2002 Tau filament formation and associative memory deficit in aged mice expressing mutant (R406 W) human tau. Proc. Natl. Acad. Sci.  USA 99, 13896–13901.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Tremblay M. A., Acker C. M. and 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. J. Alzheimers Dis. 19, 721–733.

    Article  PubMed  CAS  Google Scholar 

  • von Bergen M., Friedhoff P., Biernat J., Heberle J. and 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. Proc. Natl. Acad. Sci. USA 97, 5129–5134.

    Article  Google Scholar 

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

    Article  Google Scholar 

  • Wang Y. and Mandelkow E. 2016 Tau in physiology and pathology. Nat. Rev. Neurosci. 17, 5–21.

    Article  PubMed  CAS  Google Scholar 

  • Wang Y. P., Biernat J., Pickhardt M., Mandelkow E. and Mandelkow E. M. 2007 Stepwise proteolysis liberates tau fragments that nucleate the Alzheimer-like aggregation of full-length tau in a neuronal cell model. Proc. Natl. Acad. Sci. USA 104, 10252–10257.

  • Weingarten M. D., Lockwood A. H., Hwo S. Y. and Kirschner M. W. 1975 A protein factor essential for microtubule assembly. Proc. Natl. Acad. Sci. USA 72, 1858–1862.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

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

  • Wolfe M. S. 2009 Tau mutations in neurodegenerative diseases. J. Biol. Chem. 284, 6021–6025.

    Article  PubMed  CAS  Google Scholar 

  • Wu T. H., Lu Y. N., Chuang C. L., Wu C. L. and 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. Neuropathol. 125, 711–725.

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Acknowledgements

Research work on neurodegenerative disorders is supported by grants from the Department of Biotechnology (DBT) (ref. no. BT/PR15492/MED/122/46/2016) and Council of Scientific and Industrial Research (CSIR) (ref. no. 37(1667)/16/EMR-II), Government of India, New Delhi. Thanks to Ms Nabanita Sarkar for critically reading the manuscript and constructive suggestions.

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    Surajit Sarkar

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Sarkar, S. Neurofibrillary tangles mediated human neuronal tauopathies: insights from fly models. J Genet 97, 783–793 (2018). https://doi.org/10.1007/s12041-018-0962-4

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