Journal of Molecular Neuroscience

, Volume 65, Issue 4, pp 480–490 | Cite as

Prion-Like Propagation of Post-Translationally Modified Tau in Alzheimer’s Disease: A Hypothesis

  • Shweta Kishor Sonawane
  • Subashchandrabose ChinnathambiEmail author


The microtubule-associated protein Tau plays a key role in the neuropathology of Alzheimer’s disease by forming intracellular neurofibrillary tangles. Tau in the normal physiological condition helps stabilize microtubules and transport. Tau aggregates due to various gene mutations, intracellular insults and abnormal post-translational modifications, phosphorylation being the most important one. Other modifications which alter the function of Tau protein are glycation, nitration, acetylation, methylation, oxidation, etc. In addition to forming intracellular aggregates, Tau pathology might spread in a prion-like manner as revealed by several in vitro and in vivo studies. The possible mechanism of Tau spread can be via bulk endocytosis of misfolded Tau species. The recent studies elucidating this mechanism have mainly focussed on the aggregation and spread of repeat domain of Tau in the cell culture models. Further studies are needed to elucidate the prion-like propagation property of full-length Tau and its aggregates in a more intense manner in vitro as well as in vivo conditions. Varied post-translational modifications can have discrete effects on aggregation propensity of Tau as well as its propagation. Here, we review the prion-like properties of Tau and hypothesize the role of glycation in prion-like properties of Tau. This post-translationally modified Tau might have an enhanced propagation property due to differential properties conferred by the modifications.


Tau Post-translational modifications of tau Propagation of tau Alzheimer disease Tauopathies 



Alzheimer’s Disease


a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid


Post-translational modifications


Advanced Glycation End products


Paired helical filaments


Carboxymethyl lysine


Laminin receptor precursor


LDL receptor related protein 1


Receptor for Advanced Glycation End products


Central nervous system



Shweta Kishor Sonawane acknowledges a fellowship from the Department of Biotechnology (DBT), India. The authors acknowledge Abhishek Balmik and Nalini Vijay Gorantla for proofreading the manuscript and useful comments.


This project was supported in part by grants from the Department of Science and Technology—Science and Engineering Research Board (DST-SERB, Young Investigator grant): SB/YS/LS-355/2013, Department of Biotechnology from Neuroscience Task Force (Medical

Biotechnology-Human Development & Disease Biology (DBT-HDDB))-BT/PR/15780/MED/30/1629/2015 and in-house CSIR-National Chemical Laboratory grant MLP029526 and CSIR-network project BSC0115.

Compliance with Ethical Standards

Conflict of Interest Statement

The authors have declared no conflict of interest.


  1. Adjou KT et al (2003) A novel generation of heparan sulfate mimetics for the treatment of prion diseases. J Gen Virol 84:2595–2603CrossRefPubMedGoogle Scholar
  2. Ahmed Z et al (2014) A novel in vivo model of tau propagation with rapid and progressive neurofibrillary tangle pathology: the pattern of spread is determined by connectivity, not proximity. Acta Neuropathol 127:667–683CrossRefPubMedPubMedCentralGoogle Scholar
  3. Alonso AC, Zaidi T, Novak M, Grundke-Iqbal I, Iqbal K (2001) Hyperphosphorylation induces self-assembly of τ into tangles of paired helical filaments/straight filaments. Proc Natl Acad Sci 98:6923–6928CrossRefPubMedGoogle Scholar
  4. Alonso AC, Li B, Grundke-Iqbal I, Iqbal K (2006) Polymerization of hyperphosphorylated tau into filaments eliminates its inhibitory activity. Proc Natl Acad Sci 103:8864–8869CrossRefGoogle Scholar
  5. Alonso AD, Di Clerico J, Li B, Corbo CP, Alaniz ME, Grundke-Iqbal I, Iqbal K (2010) Phosphorylation of tau at Thr212, Thr231, and Ser262 combined causes neurodegeneration. J Biol Chem 285:30851–30860CrossRefPubMedPubMedCentralGoogle Scholar
  6. Batkulwar KB et al (2015) Investigation of phosphoproteome in RAGE signaling. Proteomics 15:245–259CrossRefPubMedGoogle Scholar
  7. Beitz J (2014) Parkinson's disease: a review. Front Biosci (Schol Ed) 6:65–74CrossRefGoogle Scholar
  8. Binder LI, Frankfurter A, Rebhun LI (1985) The distribution of tau in the mammalian central nervous system. J Cell Biol 101:1371–1378CrossRefPubMedGoogle Scholar
  9. Bolton DC, Meyer RK, Prusiner SB (1985) Scrapie PrP 27-30 is a sialoglycoprotein. J Virol 53:596–606PubMedPubMedCentralGoogle Scholar
  10. Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259CrossRefPubMedPubMedCentralGoogle Scholar
  11. Bulic B, Pickhardt M, Schmidt B, Mandelkow EM, Waldmann H, Mandelkow E (2009) Development of tau aggregation inhibitors for Alzheimer's disease. Angew Chem Int Ed 48:1740–1752CrossRefGoogle Scholar
  12. Cai Z et al (2016) Role of RAGE in Alzheimer’s disease. Cell Mol Neurobiol 36:483–495CrossRefPubMedGoogle Scholar
  13. Calafate S, Flavin W, Verstreken P, Moechars D (2016) Loss of Bin1 promotes the propagation of tau pathology. Cell Rep 17:931–940CrossRefPubMedGoogle Scholar
  14. Cancellotti E et al (2010) Glycosylation of PrPC determines timing of neuroinvasion and targeting in the brain following transmissible spongiform encephalopathy infection by a peripheral route. J Virol 84:3464–3475CrossRefPubMedPubMedCentralGoogle Scholar
  15. Cancellotti E et al (2013) Post-translational changes to PrP alter transmissible spongiform encephalopathy strain properties. EMBO J 32:756–769CrossRefPubMedPubMedCentralGoogle Scholar
  16. Caspi S, Halimi M, Yanai A, Sasson SB, Taraboulos A, Gabizon R (1998) The anti-prion activity of Congo red putative mechanism. J Biol Chem 273:3484–3489CrossRefPubMedGoogle Scholar
  17. Caughey B, Race RE, Ernst D, Buchmeier MJ, Chesebro B (1989) Prion protein biosynthesis in scrapie-infected and uninfected neuroblastoma cells. J Virol 63:175–181PubMedPubMedCentralGoogle Scholar
  18. Cho J-H, Johnson GV (2003) Glycogen synthase kinase 3β phosphorylates tau at both primed and unprimed sites. Differential impact on microtubule binding. J Biol Chem 278:187–193CrossRefPubMedGoogle Scholar
  19. Choi Y-G et al (2004) Nonenzymatic glycation at the N terminus of pathogenic prion protein in transmissible spongiform encephalopathies. J Biol Chem 279:30402–30409CrossRefPubMedGoogle Scholar
  20. Clavaguera F, Hench J, Goedert M, Tolnay M (2015) Invited review: prion-like transmission and spreading of tau pathology. Neuropathol Appl Neurobiol 41:47–58CrossRefPubMedGoogle Scholar
  21. Clavaguera F, Tolnay M, Goedert M (2016) The prion-like behavior of assembled Tau in transgenic mice. Cold Spring Harb Perspect Med 7(10):a024372Google Scholar
  22. Congdon EE, Gu J, Sait HB, Sigurdsson EM (2013) Antibody uptake into neurons occurs primarily via clathrin-dependent Fcγ receptor endocytosis and is a prerequisite for acute tau protein clearance. J Biol Chem 288:35452–35465CrossRefPubMedPubMedCentralGoogle Scholar
  23. Coppola G et al (2012) Evidence for a role of the rare p. A152T variant in MAPT in increasing the risk for FTD-spectrum and Alzheimer's diseases. Hum Mol Genet 21:3500–3512CrossRefPubMedPubMedCentralGoogle Scholar
  24. Corato M et al (2009) Doxorubicin and Congo red effectiveness on prion infectivity in golden Syrian hamster. Anticancer Res 29:2507–2512PubMedGoogle Scholar
  25. Dear DV et al (2007) Effects of post-translational modifications on prion protein aggregation and the propagation of scrapie-like characteristics in vitro. Biochim Biophys Acta (BBA)-Proteins and Proteomics 1774:792–802CrossRefGoogle Scholar
  26. Drewes G et al (1992) Mitogen activated protein (MAP) kinase transforms tau protein into an Alzheimer-like state. EMBO J 11:2131PubMedPubMedCentralCrossRefGoogle Scholar
  27. Drewes G et al (1995) Microtubule-associated protein/microtubule affinity-regulating kinase (p110mark) a novel protein kinase that regulates tau-microtubule interactions and dynamic instability by phosphorylation at the Alzheimer-specific site serine 262. J Biol Chem 270:7679–7688CrossRefPubMedGoogle Scholar
  28. D'Souza I, Schellenberg GD (2005) Regulation of tau isoform expression and dementia. Biochim Biophys Acta (BBA)-Molecular Basis of Disease 1739:104–115CrossRefGoogle Scholar
  29. Dvorakova E, Prouza M, Janouskova O, Panigaj M, Holada K (2011) Development of monoclonal antibodies specific for glycated prion protein. J Toxic Environ Health A 74:1469–1475CrossRefGoogle Scholar
  30. Eriksen JL, Wszolek Z, Petrucelli L (2005) Molecular pathogenesis of Parkinson disease. Arch Neurol 62:353–357CrossRefPubMedGoogle Scholar
  31. Fawver JN, Schall HE, Petrofes Chapa RD, Zhu X, Murray IV (2012) Amyloid-β metabolite sensing: biochemical linking of glycation modification and misfolding. J Alzheimers Dis 30:63–73CrossRefPubMedGoogle Scholar
  32. Frost B, Jacks RL, Diamond MI (2009) Propagation of tau misfolding from the outside to the inside of a cell. J Biol Chem 284:12845–12852CrossRefPubMedPubMedCentralGoogle Scholar
  33. Funk KE, Mirbaha H, Jiang H, Holtzman DM, Diamond MI (2015) Distinct therapeutic mechanisms of tau antibodies: promoting microglial clearance versus blocking neuronal uptake. J Biol Chem 290:21652–21662CrossRefPubMedPubMedCentralGoogle Scholar
  34. Gauczynski S et al (2001) The 37-kDa/67-kDa laminin receptor acts as the cell-surface receptor for the cellular prion protein. EMBO J 20:5863–5875CrossRefPubMedPubMedCentralGoogle Scholar
  35. Goedert M (2015) Alzheimer’s and Parkinson’s diseases: the prion concept in relation to assembled Aβ, tau, and α-synuclein. Science 349:1255555CrossRefPubMedGoogle Scholar
  36. Goedert M, Spillantini MG (2000) Tau mutations in frontotemporal dementia FTDP-17 and their relevance for Alzheimer’s disease. Biochim Biophys Acta (BBA)-Molecular Basis of Disease 1502:110–121CrossRefGoogle Scholar
  37. Goedert M, Spillantini M, Jakes R, Rutherford D, Crowther R (1989) Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease. Neuron 3:519–526CrossRefPubMedGoogle Scholar
  38. Goedert M, Eisenberg DS, Crowther RA (2017a) Propagation of tau aggregates and neurodegeneration Annu Rev Neurosci 40:189–210Google Scholar
  39. Goedert M, Masuda-Suzukake M, Falcon B (2017b) Like prions: the propagation of aggregated tau and α-synuclein in neurodegeneration. Brain J Neurol 140:266CrossRefGoogle Scholar
  40. Gong C-X, Liu F, Grundke-Iqbal I, Iqbal K (2005) Post-translational modifications of tau protein in Alzheimer’s disease. J Neural Transm 112:813–838CrossRefPubMedGoogle Scholar
  41. Guo JL, Lee VM-Y (2011) Seeding of normal tau by pathological tau conformers drives pathogenesis of Alzheimer-like tangles. J Biol Chem 286:15317–15331CrossRefPubMedPubMedCentralGoogle Scholar
  42. Hanger DP, Anderton BH, Noble W (2009) Tau phosphorylation: the therapeutic challenge for neurodegenerative disease. Trends Mol Med 15:112–119CrossRefPubMedGoogle Scholar
  43. Hasegawa M, Nonaka T, Masuda-Suzukake M (2017) Prion-like mechanisms and potential therapeutic targets in neurodegenerative disorders. Pharmacol Ther 172:22–33Google Scholar
  44. Heiseke A, Aguib Y, Schatzl HM (2010) Autophagy, prion infection and their mutual interactions. Curr Issues Mol Biol 12:87PubMedGoogle Scholar
  45. Holmes BB et al (2014) Proteopathic tau seeding predicts tauopathy in vivo. Proc Natl Acad Sci 111:E4376–E4385CrossRefPubMedGoogle Scholar
  46. Hong M et al (1998) Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17. Science 282:1914–1917CrossRefPubMedGoogle Scholar
  47. Hutton M et al (1998) Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393:702–705CrossRefPubMedGoogle Scholar
  48. Ingram EM, Spillantini MG (2002) Tau gene mutations: dissecting the pathogenesis of FTDP-17. Trends Mol Med 8:555–562CrossRefPubMedGoogle Scholar
  49. Ittner LM et al (2010) Dendritic function of tau mediates amyloid-β toxicity in Alzheimer's disease mouse models. Cell 142:387–397CrossRefPubMedGoogle Scholar
  50. Johnson GV, Stoothoff WH (2004) Tau phosphorylation in neuronal cell function and dysfunction. J Cell Sci 117:5721–5729CrossRefPubMedGoogle Scholar
  51. Kadavath H et al (2015) Tau stabilizes microtubules by binding at the interface between tubulin heterodimers proceedings of the, vol 112. National Academy of Sciences, pp 7501–7506Google Scholar
  52. Kaufman SK et al (2016) Tau prion strains dictate patterns of cell pathology, progression rate, and regional vulnerability in vivo. Neuron 92:796–812CrossRefPubMedPubMedCentralGoogle Scholar
  53. Kfoury N, Holmes BB, Jiang H, Holtzman DM, Diamond MI (2012) Trans-cellular propagation of tau aggregation by fibrillar species. J Biol Chem 287:19440–19451CrossRefPubMedPubMedCentralGoogle Scholar
  54. Klöhn P-C, Castro-Seoane R, Collinge J (2013) Exosome release from infected dendritic cells: a clue for a fast spread of prions in the periphery? J Infect 67:359–368CrossRefPubMedGoogle Scholar
  55. Ko L-w, Ko EC, Nacharaju P, Liu W-K, Chang E, Kenessey A, Yen S-HC (1999) An immunochemical study on tau glycation in paired helical filaments. Brain Res 830:301–313CrossRefPubMedGoogle Scholar
  56. Koriyama Y, Furukawa A, Muramatsu M, Takino J-i, Takeuchi M (2015) Glyceraldehyde caused Alzheimer’s disease-like alterations in diagnostic marker levels in SH-SY5Y human neuroblastoma cells. Sci Rep 5:13313CrossRefPubMedPubMedCentralGoogle Scholar
  57. Kurbatskaya K et al (2016) Upregulation of calpain activity precedes tau phosphorylation and loss of synaptic proteins in Alzheimer’s disease brain. Acta Neuropathol Commun 4:34CrossRefPubMedPubMedCentralGoogle Scholar
  58. Lasagna-Reeves CA et al (2012) Alzheimer brain-derived tau oligomers propagate pathology from endogenous tau. Scientific Report 2Google Scholar
  59. Lasagna-Reeves CA et al (2014) The formation of tau pore-like structures is prevalent and cell specific: possible implications for the disease phenotypes. Acta Neuropathol Commun 2(1)Google Scholar
  60. LeBoeuf AC et al (2008) FTDP-17 mutations in tau Alter the regulation of microtubule dynamics: an "alternative core" model for normal and pathological Tau action. J Biol Chem 283:36406–36415CrossRefPubMedPubMedCentralGoogle Scholar
  61. Ledesma MD, Bonay P, Colaco C, Avila J (1994) Analysis of microtubule-associated protein tau glycation in paired helical filaments. J Biol Chem 269:21614–21619PubMedGoogle Scholar
  62. Ledesma MD, Bonay P, Avila J (1995) τ protein from Alzheimer's disease patients is glycated at its tubulin-binding domain. J Neurochem 65:1658–1664CrossRefPubMedGoogle Scholar
  63. Li L, Napper S, Cashman NR (2010) Immunotherapy for prion diseases: opportunities and obstacles. Immunotherapy 2:269–282CrossRefPubMedGoogle Scholar
  64. Liu SJ et al (2004) Tau becomes a more favorable substrate for GSK-3 when it is prephosphorylated by PKA in rat brain. J Biol Chem 279:50078–50088CrossRefPubMedGoogle Scholar
  65. Liu K, Liu Y, Li L, Qin P, Iqbal J, Deng Y, Qing H (2016) Glycation alter the process of tau phosphorylation to change tau isoforms aggregation property. Biochim Biophys Acta (BBA)-Molecular Basis of Disease 1862:192–201CrossRefGoogle Scholar
  66. Lovestone S et al (2015) A phase II trial of tideglusib in Alzheimer's disease. J Alzheimers Dis 45:75–88CrossRefPubMedGoogle Scholar
  67. Mably AJ et al (2015) Tau immunization: a cautionary tale? Neurobiol Aging 36:1316–1332CrossRefPubMedGoogle Scholar
  68. Mandelkow E-M, Drewes G, Biernat J, Gustke N, Van Lint J, Jv V, Mandelkow E (1992) Glycogen synthase kinase-3 and the Alzheimer-like state of microtubule-associated protein tau. FEBS Lett 314:315–321CrossRefPubMedGoogle Scholar
  69. Margalith I et al (2012) Polythiophenes inhibit prion propagation by stabilizing prion protein (PrP) aggregates. J Biol Chem 287:18872–18887CrossRefPubMedPubMedCentralGoogle Scholar
  70. Matsuoka Y et al (2007) Intranasal NAP administration reduces accumulation of amyloid peptide and tau hyperphosphorylation in a transgenic mouse model of Alzheimer's disease at early pathological stage. J Mol Neurosci 31:165–170PubMedGoogle Scholar
  71. Mirbaha H, Holmes BB, Sanders DW, Bieschke J, Diamond MI (2015) Tau trimers are the minimal propagation unit spontaneously internalized to seed intracellular aggregation. J Biol Chem 290:14893–14903CrossRefPubMedPubMedCentralGoogle Scholar
  72. Morimoto BH, Schmechel D, Hirman J, Blackwell A, Keith J, Gold M, Investigators A--S (2013) A double-blind, placebo-controlled, ascending-dose, randomized study to evaluate the safety, tolerability and effects on cognition of AL-108 after 12 weeks of intranasal administration in subjects with mild cognitive impairment. Dement Geriatr Cogn Disord 35:325–339CrossRefPubMedGoogle Scholar
  73. Mukrasch MD, von Bergen M, Biernat J, Fischer D, Griesinger C, Mandelkow E, Zweckstetter M (2007) The “jaws” of the tau-microtubule interaction. J Biol Chem 282:12230–12239CrossRefPubMedGoogle Scholar
  74. Necula M, Kuret J (2004) Pseudophosphorylation and glycation of tau protein enhance but do not trigger fibrillization in vitro. J Biol Chem 279:49694–49703CrossRefPubMedGoogle Scholar
  75. Nicholls SB et al (2017) Characterization of TauC3 antibody and demonstration of its potential to block tau propagation. PLoS One 12:e0177914CrossRefPubMedPubMedCentralGoogle Scholar
  76. Ohgami N, Nagai R, Ikemoto M, Arai H, Kuniyasu A, Horiuchi S, Nakayama H (2001) Cd36, a member of the class b scavenger receptor family, as a receptor for advanced glycation end products. J Biol Chem 276:3195–3202CrossRefPubMedGoogle Scholar
  77. Ott C, Jacobs K, Haucke E, Santos AN, Grune T, Simm A (2014) Role of advanced glycation end products in cellular signaling. Redox Biol 2:411–429CrossRefPubMedPubMedCentralGoogle Scholar
  78. Pooler AM, Phillips EC, Lau DH, Noble W, Hanger DP (2013) Physiological release of endogenous tau is stimulated by neuronal activity. EMBO Rep 14:389–394CrossRefPubMedPubMedCentralGoogle Scholar
  79. Porto-Carreiro I, Février B, Paquet S, Vilette D, Raposo G (2005) Prions and exosomes: from PrPc trafficking to PrPsc propagation. Blood Cell Mol Dis 35:143–148CrossRefGoogle Scholar
  80. Reynolds MR, Berry RW, Binder LI (2005) Site-specific nitration differentially influences τ assembly in vitro. Biochemistry 44:13997–14009CrossRefPubMedGoogle Scholar
  81. Roettger Y, Du Y, Bacher M, Zerr I, Dodel R, Bach J-P (2013) Immunotherapy in prion disease. Nat Rev Neurol 9:98–105CrossRefPubMedGoogle Scholar
  82. Saijo E, Hughson AG, Raymond GJ, Suzuki A, Horiuchi M, Caughey B (2016) PrPSc-specific antibody reveals C-terminal conformational differences between prion strains. J Virol 90:4905–4913CrossRefPubMedPubMedCentralGoogle Scholar
  83. Sanders DW et al (2014) Distinct tau prion strains propagate in cells and mice and define different tauopathies. Neuron 82:1271–1288CrossRefPubMedPubMedCentralGoogle Scholar
  84. 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. Biochemistry 38:3549–3558CrossRefPubMedGoogle Scholar
  85. Schweers O, Schönbrunn-Hanebeck E, Marx A, Mandelkow E (1994) Structural studies of tau protein and Alzheimer paired helical filaments show no evidence for beta-structure. J Biol Chem 269:24290–24297PubMedGoogle Scholar
  86. Selkoe DJ (2001) Alzheimer's disease: genes, proteins, and therapy. Physiol Rev 81:741–766CrossRefPubMedGoogle Scholar
  87. Shyng S-L, Heuser JE, Harris DA (1994) A glycolipid-anchored prion protein is endocytosed via clathrin-coated pits. J Cell Biol 125:1239–1250CrossRefPubMedGoogle Scholar
  88. Song L et al (2015) Analysis of tau post-translational modifications in rTg4510 mice, a model of tau pathology. Mol Neurodegener 10:14CrossRefPubMedPubMedCentralGoogle Scholar
  89. Steinhilb ML, Dias-Santagata D, Fulga TA, Felch DL, Feany MB (2007) Tau phosphorylation sites work in concert to promote neurotoxicity in vivo. Mol Biol Cell 18:5060–5068CrossRefPubMedPubMedCentralGoogle Scholar
  90. Sydow A, Mandelkow E-M (2010) Prion-like propagation of mouse and human tau aggregates in an inducible mouse model of tauopathy. Neurodegener Dis 7:28–31CrossRefPubMedGoogle Scholar
  91. Takeda S et al (2015) Neuronal uptake and propagation of a rare phosphorylated high-molecular-weight tau derived from Alzheimer's disease brain. Nat Commun 6:8490CrossRefPubMedPubMedCentralGoogle Scholar
  92. Taylor DR, Hooper NM (2007) The low-density lipoprotein receptor-related protein 1 (LRP1) mediates the endocytosis of the cellular prion protein. Biochem J 402:17–23CrossRefPubMedPubMedCentralGoogle Scholar
  93. Tiwari SS et al (2016) Alzheimer-related decrease in CYFIP2 links amyloid production to tau hyperphosphorylation and memory loss. Brain 139:2751–2765CrossRefPubMedPubMedCentralGoogle Scholar
  94. Tseng H-C, Lu Q, Henderson E, Graves DJ (1999) Phosphorylated tau can promote tubulin assembly. Proc Natl Acad Sci 96:9503–9508CrossRefPubMedGoogle Scholar
  95. Vella L, Sharples R, Lawson V, Masters C, Cappai R, Hill A (2007) Packaging of prions into exosomes is associated with a novel pathway of PrP processing. J Pathol 211:582–590CrossRefPubMedGoogle Scholar
  96. Walker LC, Diamond MI, Duff KE, Hyman BT (2013) Mechanisms of protein seeding in neurodegenerative diseases. JAMA Neurol 70:304–310CrossRefPubMedGoogle Scholar
  97. Wang Y, Mandelkow E (2016) Tau in physiology and pathology. Nat Rev Neurosci 17:22–35CrossRefGoogle Scholar
  98. Wegmann S, Nicholls S, Takeda S, Fan Z, Hyman BT (2016) Formation, release, and internalization of stable tau oligomers in cells. J Neurochem 139:1163–1174CrossRefPubMedPubMedCentralGoogle Scholar
  99. Wei Y, Han C, Wang Y, Wu B, Su T, Liu Y, He R (2015) Ribosylation triggering Alzheimer's disease-like tau hyperphosphorylation via activation of CaMKII. Aging Cell 14:754–763CrossRefPubMedPubMedCentralGoogle Scholar
  100. Weingarten MD, Lockwood AH, Hwo S-Y, Kirschner MW (1975) A protein factor essential for microtubule assembly. Proc Natl Acad Sci 72:1858–1862CrossRefPubMedGoogle Scholar
  101. Wu JW et al (2013) Small misfolded tau species are internalized via bulk endocytosis and anterogradely and retrogradely transported in neurons. J Biol Chem 288:1856–1870CrossRefPubMedGoogle Scholar
  102. Wu JW et al (2016) Neuronal activity enhances tau propagation and tau pathology in vivo. Nat Neurosci 19:1085–1092CrossRefPubMedPubMedCentralGoogle Scholar
  103. Xu L, Zheng J, Margittai M, Nussinov R, Ma B (2016) How does hyperphopsphorylation promote tau aggregation and modulate filament structure and stability? ACS Chem Neurosci 7:565–575CrossRefPubMedGoogle Scholar
  104. Yan S et al (1994) Glycated tau protein in Alzheimer disease: a mechanism for induction of oxidant stress. Proc Natl Acad Sci 91:7787–7791CrossRefPubMedGoogle Scholar

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Authors and Affiliations

  1. 1.Neurobiology Group, Division of Biochemical SciencesCSIR-National Chemical LaboratoryPuneIndia
  2. 2.Academy of Scientific and Innovative Research (AcSIR)New DelhiIndia

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