Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Molecular Mechanism of Tau Misfolding and Aggregation: Insights from Molecular Dynamics Simulation

Author(s): Haiyang Zhong, Hongli Liu and Huanxiang Liu*

Volume 31, Issue 20, 2024

Published on: 21 June, 2023

Page: [2855 - 2871] Pages: 17

DOI: 10.2174/0929867330666230409145247

Price: $65

Abstract

Tau dysfunction has a close association with many neurodegenerative diseases, which are collectively referred to as tauopathies. Neurofibrillary tangles (NFTs) formed by misfolding and aggregation of tau are the main pathological process of tauopathy. Therefore, uncovering the misfolding and aggregation mechanism of tau protein will help to reveal the pathogenic mechanism of tauopathies. Molecular dynamics (MD) simulation is well suited for studying the dynamic process of protein structure changes. It provides detailed information on protein structure changes over time at the atomic resolution. At the same time, MD simulation can also simulate various conditions conveniently. Based on these advantages, MD simulations are widely used to study conformational transition problems such as protein misfolding and aggregation. Here, we summarized the structural features of tau, the factors affecting its misfolding and aggregation, and the applications of MD simulations in the study of tau misfolding and aggregation.

Keywords: Tau protein, aggregation, misfolding, molecular dynamics simulation, post-translational modifications, mutation.

« Previous Next »
[1]
Weingarten, M.D.; Lockwood, A.H.; Hwo, S.Y.; Kirschner, M.W. A protein factor essential for microtubule assembly. Proc. Natl. Acad. Sci. USA, 1975, 72(5), 1858-1862.
[http://dx.doi.org/10.1073/pnas.72.5.1858] [PMID: 1057175]
[2]
Kosik, K.S. The molecular and cellular biology of tau. Brain Pathol., 1993, 3(1), 39-43.
[http://dx.doi.org/10.1111/j.1750-3639.1993.tb00724.x] [PMID: 8269082]
[3]
Gustke, N.; Trinczek, B.; Biernat, J.; Mandelkow, E.M.; Mandelkow, E. Domains of tau protein and interactions with microtubules. Biochemistry, 1994, 33(32), 9511-9522.
[http://dx.doi.org/10.1021/bi00198a017] [PMID: 8068626]
[4]
Andreadis, A. Misregulation of tau alternative splicing in neurodegeneration and dementia. Prog. Mol. Subcell. Biol., 2006, 44, 89-107.
[http://dx.doi.org/10.1007/978-3-540-34449-0_5] [PMID: 17076266]
[5]
Goedert, M.; Spillantini, M.G.; Jakes, R.; Rutherford, D.; Crowther, R.A. Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer’s disease. Neuron, 1989, 3(4), 519-526.
[http://dx.doi.org/10.1016/0896-6273(89)90210-9] [PMID: 2484340]
[6]
Lee, V.M.Y.; Goedert, M.; Trojanowski, J.Q. Neurodegenerative tauopathies. Annu. Rev. Neurosci., 2001, 24(1), 1121-1159.
[http://dx.doi.org/10.1146/annurev.neuro.24.1.1121] [PMID: 11520930]
[7]
Morris, M.; Maeda, S.; Vossel, K.; Mucke, L. The many faces of tau. Neuron, 2011, 70(3), 410-426.
[http://dx.doi.org/10.1016/j.neuron.2011.04.009] [PMID: 21555069]
[8]
Cleveland, D.W.; Hwo, S.Y.; Kirschner, M.W. Physical and chemical properties of purified tau factor and the role of tau in microtubule assembly. J. Mol. Biol., 1977, 116(2), 227-247.
[http://dx.doi.org/10.1016/0022-2836(77)90214-5] [PMID: 146092]
[9]
Skrabana, R.; Sevcik, J.; Novak, M. Intrinsically disordered proteins in the neurodegenerative processes: formation of tau protein paired helical filaments and their analysis. Cell. Mol. Neurobiol., 2006, 26(7-8), 1083-1095.
[http://dx.doi.org/10.1007/s10571-006-9083-3] [PMID: 16779670]
[10]
Jeganathan, S.; von Bergen, M.; Brutlach, H.; Steinhoff, H.J.; Mandelkow, E. Global hairpin folding of tau in solution. Biochemistry, 2006, 45(7), 2283-2293.
[http://dx.doi.org/10.1021/bi0521543] [PMID: 16475817]
[11]
Irwin, D.J.; Cohen, T.J.; Grossman, M.; Arnold, S.E.; Xie, S.X.; Lee, V.M.Y.; Trojanowski, J.Q. Acetylated tau, a novel pathological signature in Alzheimer’s disease and other tauopathies. Brain, 2012, 135(3), 807-818.
[http://dx.doi.org/10.1093/brain/aws013] [PMID: 22366796]
[12]
Alonso, A.C.; Grundke-Iqbal, I.; Iqbal, K. Alzheimer’s disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules. Nat. Med., 1996, 2(7), 783-787.
[http://dx.doi.org/10.1038/nm0796-783] [PMID: 8673924]
[13]
Haase, C.; Stieler, J.T.; Arendt, T.; Holzer, M. Pseudophosphorylation of tau protein alters its ability for self-aggregation. J. Neurochem., 2004, 88(6), 1509-1520.
[http://dx.doi.org/10.1046/j.1471-4159.2003.02287.x] [PMID: 15009652]
[14]
Huvent, I.; Kamah, A.; Cantrelle, F.X.; Barois, N.; Slomianny, C.; Smet-Nocca, C.; Landrieu, I.; Lippens, G. A functional fragment of Tau forms fibers without the need for an intermolecular cysteine bridge. Biochem. Biophys. Res. Commun., 2014, 445(2), 299-303.
[http://dx.doi.org/10.1016/j.bbrc.2014.01.161] [PMID: 24502945]
[15]
Fitzpatrick, A.W.P.; Falcon, B.; He, S.; Murzin, A.G.; Murshudov, G.; Garringer, H.J.; Crowther, R.A.; Ghetti, B.; Goedert, M.; Scheres, S.H.W. Cryo-EM structures of tau filaments from Alzheimer’s disease. Nature, 2017, 547(7662), 185-190.
[http://dx.doi.org/10.1038/nature23002] [PMID: 28678775]
[16]
Falcon, B.; Zhang, W.; Murzin, A.G.; Murshudov, G.; Garringer, H.J.; Vidal, R.; Crowther, R.A.; Ghetti, B.; Scheres, S.H.W.; Goedert, M. Structures of filaments from Pick’s disease reveal a novel tau protein fold. Nature, 2018, 561(7721), 137-140.
[http://dx.doi.org/10.1038/s41586-018-0454-y] [PMID: 30158706]
[17]
Falcon, B.; Zivanov, J.; Zhang, W.; Murzin, A.G.; Garringer, H.J.; Vidal, R.; Crowther, R.A.; Newell, K.L.; Ghetti, B.; Goedert, M.; Scheres, S.H.W. Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules. Nature, 2019, 568(7752), 420-423.
[http://dx.doi.org/10.1038/s41586-019-1026-5] [PMID: 30894745]
[18]
Zhang, W.; Falcon, B.; Murzin, A.G.; Fan, J.; Crowther, R.A.; Goedert, M.; Scheres, S.H.W. Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer’s and Pick’s diseases. eLife, 2019, 8, e43584.
[http://dx.doi.org/10.7554/eLife.43584] [PMID: 30720432]
[19]
Auer, I.A.; Schmidt, M.L.; Lee, V.M.Y.; Curry, B.; Suzuki, K.; Shin, R.W.; Pentchev, P.G.; Carstea, E.D.; Trojanowski, J.Q. Paired helical filament tau (PHFtau) in Niemann-Pick type C disease is similar to PHFtau in Alzheimer’s disease. Acta Neuropathol., 1995, 90(6), 547-551.
[http://dx.doi.org/10.1007/BF00318566] [PMID: 8615074]
[20]
Goedert, M.; Klug, A.; Crowther, R.A. Tau protein, the paired helical filament and Alzheimer’s disease. J. Alzheimers Dis., 2006, 9(s3)(Suppl.), 195-207.
[http://dx.doi.org/10.3233/JAD-2006-9S323] [PMID: 16914859]
[21]
Goedert, M.; Klug, A. Tau protein and the paired helical filament of Alzheimer’s disease. Brain Res. Bull., 1999, 50(5-6), 469-470.
[http://dx.doi.org/10.1016/S0361-9230(99)00138-0] [PMID: 10643488]
[22]
Yang, L.; Ksiezak-Reding, H. Ubiquitin immunoreactivity of paired helical filaments differs in Alzheimer’s disease and corticobasal degeneration. Acta Neuropathol., 1998, 96(5), 520-526.
[http://dx.doi.org/10.1007/s004010050928] [PMID: 9829817]
[23]
Morris, R.G.; Kopelman, M.D. The memory deficits in Alzheimer-type dementia: a review. Q. J. Exp. Psychol. A, 1986, 38(4), 575-602.
[http://dx.doi.org/10.1080/14640748608401615] [PMID: 3544082]
[24]
2022 Alzheimer’s disease facts and figures. Alzheimers Dement., 2022, 18(4), 700-789.
[http://dx.doi.org/10.1002/alz.12638] [PMID: 35289055]
[25]
Ittner, L.M.; Götz, J. Amyloid-β and tau-a toxic pas de deux in Alzheimer’s disease. Nat. Rev. Neurosci., 2011, 12(2), 67-72.
[http://dx.doi.org/10.1038/nrn2967] [PMID: 21193853]
[26]
Hardy, J.A.; Higgins, G.A. Alzheimer’s disease: The amyloid cascade hypothesis. Science, 1992, 256(5054), 184-185.
[http://dx.doi.org/10.1126/science.1566067] [PMID: 1566067]
[27]
Aisen, P.S.; Saumier, D.; Briand, R.; Laurin, J.; Gervais, F.; Tremblay, P.; Garceau, D. A Phase II study targeting amyloid- with 3APS in mild-to-moderate Alzheimer disease. Neurology, 2006, 67(10), 1757-1763.
[http://dx.doi.org/10.1212/01.wnl.0000244346.08950.64] [PMID: 17082468]
[28]
Wilcock, G.K.; Black, S.E.; Hendrix, S.B.; Zavitz, K.H.; Swabb, E.A.; Laughlin, M.A. Efficacy and safety of tarenflurbil in mild to moderate Alzheimer’s disease: a randomised phase II trial. Lancet Neurol., 2008, 7(6), 483-493.
[http://dx.doi.org/10.1016/S1474-4422(08)70090-5] [PMID: 18450517]
[29]
Ryan, J.M.; Grundman, M. Anti-amyloid-β immunotherapy in Alzheimer’s disease: ACC-001 clinical trials are ongoing. J. Alzheimers Dis., 2009, 17(2), 243-243.
[http://dx.doi.org/10.3233/JAD-2009-1118] [PMID: 19502708]
[30]
Mudher, A.; Lovestone, S. Alzheimer’s disease-do tauists and baptists finally shake hands? Trends Neurosci., 2002, 25(1), 22-26.
[http://dx.doi.org/10.1016/S0166-2236(00)02031-2] [PMID: 11801334]
[31]
Arriagada, P.V.; Marzloff, K.; Hyman, B.T. Distribution of Alzheimer-type pathologic changes in nondemented elderly individuals matches the pattern in Alzheimer’s disease. Neurology, 1992, 42(9), 1681-1688.
[http://dx.doi.org/10.1212/WNL.42.9.1681] [PMID: 1307688]
[32]
Goedert, M.; Eisenberg, D.S.; Crowther, R.A. Propagation of tau aggregates and neurodegeneration. Annu. Rev. Neurosci., 2017, 40(1), 189-210.
[http://dx.doi.org/10.1146/annurev-neuro-072116-031153] [PMID: 28772101]
[33]
Li, C.; Götz, J. Tau-based therapies in neurodegeneration: opportunities and challenges. Nat. Rev. Drug Discov., 2017, 16(12), 863-883.
[http://dx.doi.org/10.1038/nrd.2017.155] [PMID: 28983098]
[34]
de Calignon, A.; Polydoro, M.; Suárez-Calvet, M.; William, C.; Adamowicz, D.H.; Kopeikina, K.J.; Pitstick, R.; Sahara, N.; Ashe, K.H.; Carlson, G.A.; Spires-Jones, T.L.; Hyman, B.T. Propagation of tau pathology in a model of early Alzheimer’s disease. Neuron, 2012, 73(4), 685-697.
[http://dx.doi.org/10.1016/j.neuron.2011.11.033] [PMID: 22365544]
[35]
Kosik, K.S.; Joachim, C.L.; Selkoe, D.J. Microtubule-associated protein tau (tau) is a major antigenic component of paired helical filaments in Alzheimer disease. Proc. Natl. Acad. Sci. USA, 1986, 83(11), 4044-4048.
[http://dx.doi.org/10.1073/pnas.83.11.4044] [PMID: 2424016]
[36]
Chiti, F.; Dobson, C.M. Protein misfolding, functional amyloid, and human disease. Annu. Rev. Biochem., 2006, 75(1), 333-366.
[http://dx.doi.org/10.1146/annurev.biochem.75.101304.123901] [PMID: 16756495]
[37]
Hofrichter, J.; Ross, P.D.; Eaton, W.A. Kinetics and mechanism of deoxyhemoglobin S gelation: a new approach to understanding sickle cell disease. Proc. Natl. Acad. Sci. USA, 1974, 71(12), 4864-4868.
[http://dx.doi.org/10.1073/pnas.71.12.4864] [PMID: 4531026]
[38]
Lee, C.C.; Nayak, A.; Sethuraman, A.; Belfort, G.; McRae, G.J. A three-stage kinetic model of amyloid fibrillation. Biophys. J., 2007, 92(10), 3448-3458.
[http://dx.doi.org/10.1529/biophysj.106.098608] [PMID: 17325005]
[39]
Nguyen, P.H.; Li, M.S.; Stock, G.; Straub, J.E.; Thirumalai, D. Monomer adds to preformed structured oligomers of Aβ-peptides by a two-stage dock–lock mechanism. Proc. Natl. Acad. Sci. USA, 2007, 104(1), 111-116.
[http://dx.doi.org/10.1073/pnas.0607440104] [PMID: 17190811]
[40]
Lee, H.E.; Lim, D.; Lee, J.Y.; Lim, S.M.; Pae, A.N. Recent tau-targeted clinical strategies for the treatment of Alzheimer’s disease. Future Med. Chem., 2019, 11(15), 1845-1848.
[http://dx.doi.org/10.4155/fmc-2019-0151] [PMID: 31517533]
[41]
Jucker, M.; Walker, L.C. Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature, 2013, 501(7465), 45-51.
[http://dx.doi.org/10.1038/nature12481] [PMID: 24005412]
[42]
Lasagna-Reeves, C.A.; Castillo-Carranza, D.L.; Sengupta, U.; Sarmiento, J.; Troncoso, J.; Jackson, G.R.; Kayed, R. Identification of oligomers at early stages of tau aggregation in Alzheimer’s disease. FASEB J., 2012, 26(5), 1946-1959.
[http://dx.doi.org/10.1096/fj.11-199851] [PMID: 22253473]
[43]
Sharma, A.M.; Thomas, T.L.; Woodard, D.R.; Kashmer, O.M.; Diamond, M.I. Tau monomer encodes strains. eLife, 2018, 7, e37813.
[http://dx.doi.org/10.7554/eLife.37813] [PMID: 30526844]
[44]
Schweers, O.; Mandelkow, E.M.; Biernat, J.; Mandelkow, E. Oxidation of cysteine-322 in the repeat domain of microtubule-associated protein tau controls the in vitro assembly of paired helical filaments. Proc. Natl. Acad. Sci. USA, 1995, 92(18), 8463-8467.
[http://dx.doi.org/10.1073/pnas.92.18.8463] [PMID: 7667312]
[45]
Ghosh, P.; Vaidya, A.; Kumar, A.; Rangachari, V. Determination of critical nucleation number for a single nucleation amyloid-β aggregation model. Math. Biosci., 2016, 273, 70-79.
[http://dx.doi.org/10.1016/j.mbs.2015.12.004] [PMID: 26774039]
[46]
von Bergen, M.; Friedhoff, P.; Biernat, J.; Heberle, J.; Mandelkow, E.M.; Mandelkow, E. Assembly of τ protein into Alzheimer paired helical filaments depends on a local sequence motif ( 306 VQIVYK 311 ) forming β structure. Proc. Natl. Acad. Sci. USA, 2000, 97(10), 5129-5134.
[http://dx.doi.org/10.1073/pnas.97.10.5129] [PMID: 10805776]
[47]
Daebel, V.; Chinnathambi, S.; Biernat, J.; Schwalbe, M.; Habenstein, B.; Loquet, A.; Akoury, E.; Tepper, K.; Müller, H.; Baldus, M.; Griesinger, C.; Zweckstetter, M.; Mandelkow, E.; Vijayan, V.; Lange, A. β-Sheet core of tau paired helical filaments revealed by solid-state NMR. J. Am. Chem. Soc., 2012, 134(34), 13982-13989.
[http://dx.doi.org/10.1021/ja305470p] [PMID: 22862303]
[48]
Seidler, P.M.; Boyer, D.R.; Rodriguez, J.A.; Sawaya, M.R.; Cascio, D.; Murray, K.; Gonen, T.; Eisenberg, D.S. Structure-based inhibitors of tau aggregation. Nat. Chem., 2018, 10(2), 170-176.
[http://dx.doi.org/10.1038/nchem.2889] [PMID: 29359764]
[49]
von Bergen, M.; Barghorn, S.; Jeganathan, S.; Mandelkow, E.M.; Mandelkow, E. Spectroscopic approaches to the conformation of tau protein in solution and in paired helical filaments. Neurodegener. Dis., 2006, 3(4-5), 197-206.
[http://dx.doi.org/10.1159/000095257] [PMID: 17047358]
[50]
Liu, H.; Zhong, H.; Xu, Z.; Zhang, Q.; Shah, S.J.A.; Liu, H.; Yao, X. The misfolding mechanism of the key fragment R3 of tau protein: a combined molecular dynamics simulation and Markov state model study. Phys. Chem. Chem. Phys., 2020, 22(19), 10968-10980.
[http://dx.doi.org/10.1039/C9CP06954B] [PMID: 32392276]
[51]
von Bergen, M.; Barghorn, S.; Li, L.; Marx, A.; Biernat, J.; Mandelkow, E.M.; Mandelkow, E. Mutations of tau protein in frontotemporal dementia promote aggregation of paired helical filaments by enhancing local β-structure. J. Biol. Chem., 2001, 276(51), 48165-48174.
[http://dx.doi.org/10.1074/jbc.M105196200] [PMID: 11606569]
[52]
Ganguly, P.; Do, T.D.; Larini, L.; LaPointe, N.E.; Sercel, A.J.; Shade, M.F.; Feinstein, S.C.; Bowers, M.T.; Shea, J.E. Tau assembly: The dominant role of PHF6 (VQIVYK) in microtubule binding region repeat R3. J. Phys. Chem. B, 2015, 119(13), 4582-4593.
[http://dx.doi.org/10.1021/acs.jpcb.5b00175] [PMID: 25775228]
[53]
Schwalbe, M.; Kadavath, H.; Biernat, J.; Ozenne, V.; Blackledge, M.; Mandelkow, E.; Zweckstetter, M. Structural impact of tau phosphorylation at threonine 231. Structure, 2015, 23(8), 1448-1458.
[http://dx.doi.org/10.1016/j.str.2015.06.002] [PMID: 26165593]
[54]
Martin, L.; Latypova, X.; Terro, F. Post-translational modifications of tau protein: Implications for Alzheimer’s disease. Neurochem. Int., 2011, 58(4), 458-471.
[http://dx.doi.org/10.1016/j.neuint.2010.12.023] [PMID: 21215781]
[55]
Gong, C.X.; Liu, F.; Grundke-Iqbal, I.; Iqbal, K. Post-translational modifications of tau protein in Alzheimer’s disease. J. Neural Transm., 2005, 112(6), 813-838.
[http://dx.doi.org/10.1007/s00702-004-0221-0] [PMID: 15517432]
[56]
Wesseling, H.; Mair, W.; Kumar, M.; Schlaffner, C.N.; Tang, S.; Beerepoot, P.; Fatou, B.; Guise, A.J.; Cheng, L.; Takeda, S.; Muntel, J.; Rotunno, M.S.; Dujardin, S.; Davies, P.; Kosik, K.S.; Miller, B.L.; Berretta, S.; Hedreen, J.C.; Grinberg, L.T.; Seeley, W.W.; Hyman, B.T.; Steen, H.; Steen, J.A. Tau PTM profiles identify patient heterogeneity and stages of Alzheimer’s disease. Cell, 2020, 183(6), 1699-1713.e13.
[http://dx.doi.org/10.1016/j.cell.2020.10.029] [PMID: 33188775]
[57]
Craven, K.M.; Kochen, W.R.; Hernandez, C.M.; Flinn, J.M. Zinc exacerbates tau pathology in a tau mouse model. J. Alzheimers Dis., 2018, 64(2), 617-630.
[http://dx.doi.org/10.3233/JAD-180151] [PMID: 29914030]
[58]
Goedert, M.; Jakes, R.; Spillantini, M.G.; Hasegawa, M.; Smith, M.J.; Crowther, R.A. Assembly of microtubule-associated protein tau into Alzheimer-like filaments induced by sulphated glycosaminoglycans. Nature, 1996, 383(6600), 550-553.
[http://dx.doi.org/10.1038/383550a0] [PMID: 8849730]
[59]
Haj-Yahya, M.; Lashuel, H.A. Protein semisynthesis protein semisynthesis provides access to tau disease-associated post-translational modifications (PTMs) and paves the way to deciphering the tau PTM code in health and diseased states. J. Am. Chem. Soc., 2018, 140(21), 6611-6621.
[http://dx.doi.org/10.1021/jacs.8b02668] [PMID: 29684271]
[60]
Alonso, A.C.; Zaidi, T.; Novak, M.; Grundke-Iqbal, I.; Iqbal, K. Hyperphosphorylation induces self-assembly of τ into tangles of paired helical filaments/straight filaments. Proc. Natl. Acad. Sci. USA, 2001, 98(12), 6923-6928.
[http://dx.doi.org/10.1073/pnas.121119298] [PMID: 11381127]
[61]
Cohen, T.J.; Guo, J.L.; Hurtado, D.E.; Kwong, L.K.; Mills, I.P.; Trojanowski, J.Q.; Lee, V.M.Y. The acetylation of tau inhibits its function and promotes pathological tau aggregation. Nat. Commun., 2011, 2(1), 252.
[http://dx.doi.org/10.1038/ncomms1255] [PMID: 21427723]
[62]
Thomas, S.N.; Funk, K.E.; Wan, Y.; Liao, Z.; Davies, P.; Kuret, J.; Yang, A.J. Dual modification of Alzheimer’s disease PHF-tau protein by lysine methylation and ubiquitylation: A mass spectrometry approach. Acta Neuropathol., 2012, 123(1), 105-117.
[http://dx.doi.org/10.1007/s00401-011-0893-0] [PMID: 22033876]
[63]
Arnold, C.S.; Johnson, G.W.; Cole, R.N.; Dong, D.L.Y.; Lee, M.; Hart, G.W. The microtubule-associated protein tau is extensively modified with O-linked N-acetylglucosamine. J. Biol. Chem., 1996, 271(46), 28741-28744.
[http://dx.doi.org/10.1074/jbc.271.46.28741] [PMID: 8910513]
[64]
Dorval, V.; Fraser, P.E. Small ubiquitin-like modifier (SUMO) modification of natively unfolded proteins tau and α-synuclein. J. Biol. Chem., 2006, 281(15), 9919-9924.
[http://dx.doi.org/10.1074/jbc.M510127200] [PMID: 16464864]
[65]
Hanger, D.P.; Anderton, B.H.; Noble, W. Tau phosphorylation: the therapeutic challenge for neurodegenerative disease. Trends Mol. Med., 2009, 15(3), 112-119.
[http://dx.doi.org/10.1016/j.molmed.2009.01.003] [PMID: 19246243]
[66]
Hasegawa, M.; Jakes, R.; Crowther, R.A.; Lee, V.M.Y.; Ihara, Y.; Goedert, M. Characterization of mAb AP422, a novel phosphorylation-dependent monoclonal antibody against tau protein. FEBS Lett., 1996, 384(1), 25-30.
[http://dx.doi.org/10.1016/0014-5793(96)00271-2] [PMID: 8797796]
[67]
Wada, Y.; Ishiguro, K.; Itoh, T.J.; Uchida, T.; Hotani, H.; Saito, T.; Kishimoto, T.; Hisanaga, S. Microtubule-stimulated phosphorylation of tau at Ser202 and Thr205 by cdk5 decreases its microtubule nucleation activity. J. Biochem., 1998, 124(4), 738-746.
[http://dx.doi.org/10.1093/oxfordjournals.jbchem.a022174] [PMID: 9756618]
[68]
Xia, Y.; Prokop, S.; Gorion, K.M.M.; Kim, J.D.; Sorrentino, Z.A.; Bell, B.M.; Manaois, A.N.; Chakrabarty, P.; Davies, P.; Giasson, B.I. Tau Ser208 phosphorylation promotes aggregation and reveals neuropathologic diversity in Alzheimer’s disease and other tauopathies. Acta Neuropathol. Commun., 2020, 8(1), 88.
[http://dx.doi.org/10.1186/s40478-020-00967-w] [PMID: 32571418]
[69]
Despres, C.; Byrne, C.; Qi, H.; Cantrelle, F.X.; Huvent, I.; Chambraud, B.; Baulieu, E.E.; Jacquot, Y.; Landrieu, I.; Lippens, G.; Smet-Nocca, C. Identification of the Tau phosphorylation pattern that drives its aggregation. Proc. Natl. Acad. Sci. USA, 2017, 114(34), 9080-9085.
[http://dx.doi.org/10.1073/pnas.1708448114] [PMID: 28784767]
[70]
Shin, M.K.; Vázquez-Rosa, E.; Koh, Y.; Dhar, M.; Chaubey, K.; Cintrón-Pérez, C.J.; Barker, S.; Miller, E.; Franke, K.; Noterman, M.F.; Seth, D.; Allen, R.S.; Motz, C.T.; Rao, S.R.; Skelton, L.A.; Pardue, M.T.; Fliesler, S.J.; Wang, C.; Tracy, T.E.; Gan, L.; Liebl, D.J.; Savarraj, J.P.J.; Torres, G.L.; Ahnstedt, H.; McCullough, L.D.; Kitagawa, R.S.; Choi, H.A.; Zhang, P.; Hou, Y.; Chiang, C.W.; Li, L.; Ortiz, F.; Kilgore, J.A.; Williams, N.S.; Whitehair, V.C.; Gefen, T.; Flanagan, M.E.; Stamler, J.S.; Jain, M.K.; Kraus, A.; Cheng, F.; Reynolds, J.D.; Pieper, A.A. Reducing acetylated tau is neuroprotective in brain injury. Cell, 2021, 184(10), 2715-2732.e23.
[http://dx.doi.org/10.1016/j.cell.2021.03.032] [PMID: 33852912]
[71]
Tracy, T.E.; Sohn, P.D.; Minami, S.S.; Wang, C.; Min, S.W.; Li, Y.; Zhou, Y.; Le, D.; Lo, I.; Ponnusamy, R.; Cong, X.; Schilling, B.; Ellerby, L.M.; Huganir, R.L.; Gan, L. Acetylated tau obstructs KIBRA-mediated signaling in synaptic plasticity and promotes tauopathy-related memory loss. Neuron, 2016, 90(2), 245-260.
[http://dx.doi.org/10.1016/j.neuron.2016.03.005] [PMID: 27041503]
[72]
Luo, H.B.; Xia, Y.Y.; Shu, X.J.; Liu, Z.C.; Feng, Y.; Liu, X.H.; Yu, G.; Yin, G.; Xiong, Y.S.; Zeng, K.; Jiang, J.; Ye, K.; Wang, X.C.; Wang, J.Z. SUMOylation at K340 inhibits tau degradation through deregulating its phosphorylation and ubiquitination. Proc. Natl. Acad. Sci. USA, 2014, 111(46), 16586-16591.
[http://dx.doi.org/10.1073/pnas.1417548111] [PMID: 25378699]
[73]
Clark, L.N.; Poorkaj, P.; Wszolek, Z.; Geschwind, D.H.; Nasreddine, Z.S.; Miller, B.; Li, D.; Payami, H.; Awert, F.; Markopoulou, K.; Andreadis, A.; D’Souza, I.; Lee, V.M.Y.; Reed, L.; Trojanowski, J.Q.; Zhukareva, V.; Bird, T.; Schellenberg, G.; Wilhelmsen, K.C. Pathogenic implications of mutations in the tau gene in pallido-ponto-nigral degeneration and related neurodegenerative disorders linked to chromosome 17. Proc. Natl. Acad. Sci. USA, 1998, 95(22), 13103-13107.
[http://dx.doi.org/10.1073/pnas.95.22.13103] [PMID: 9789048]
[74]
Coppola, G.; Chinnathambi, S.; Lee, J.J.; Dombroski, B.A.; Baker, M.C.; Soto-Ortolaza, A.I.; Lee, S.E.; Klein, E.; Huang, A.Y.; Sears, R.; Lane, J.R.; Karydas, A.M.; Kenet, R.O.; Biernat, J.; Wang, L.S.; Cotman, C.W.; DeCarli, C.S.; Levey, A.I.; Ringman, J.M.; Mendez, M.F.; Chui, H.C.; Le Ber, I.; Brice, A.; Lupton, M.K.; Preza, E.; Lovestone, S.; Powell, J.; Graff-Radford, N.; Petersen, R.C.; Boeve, B.F.; Lippa, C.F.; Bigio, E.H.; Mackenzie, I.; Finger, E.; Kertesz, A.; Caselli, R.J.; Gearing, M.; Juncos, J.L.; Ghetti, B.; Spina, S.; Bordelon, Y.M.; Tourtellotte, W.W.; Frosch, M.P.; Vonsattel, J.P.G.; Zarow, C.; Beach, T.G.; Albin, R.L.; Lieberman, A.P.; Lee, V.M.; Trojanowski, J.Q.; Van Deerlin, V.M.; Bird, T.D.; Galasko, D.R.; Masliah, E.; White, C.L.; Troncoso, J.C.; Hannequin, D.; Boxer, A.L.; Geschwind, M.D.; Kumar, S.; Mandelkow, E.M.; Wszolek, Z.K.; Uitti, R.J.; Dickson, D.W.; Haines, J.L.; Mayeux, R.; Pericak-Vance, M.A.; Farrer, L.A.; Ross, O.A.; Rademakers, R.; Schellenberg, G.D.; Miller, B.L.; Mandelkow, E.; Geschwind, D.H. 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., 2012, 21(15), 3500-3512.
[http://dx.doi.org/10.1093/hmg/dds161] [PMID: 22556362]
[75]
Kouri, N.; Carlomagno, Y.; Baker, M.; Liesinger, A.M.; Caselli, R.J.; Wszolek, Z.K.; Petrucelli, L.; Boeve, B.F.; Parisi, J.E.; Josephs, K.A.; Uitti, R.J.; Ross, O.A.; Graff-Radford, N.R.; DeTure, M.A.; Dickson, D.W.; Rademakers, R. Novel mutation in MAPT exon 13 (p.N410H) causes corticobasal degeneration. Acta Neuropathol., 2014, 127(2), 271-282.
[http://dx.doi.org/10.1007/s00401-013-1193-7] [PMID: 24121548]
[76]
Hasegawa, M.; Smith, M.J.; Goedert, M. Tau proteins with FTDP-17 mutations have a reduced ability to promote microtubule assembly. FEBS Lett., 1998, 437(3), 207-210.
[http://dx.doi.org/10.1016/S0014-5793(98)01217-4] [PMID: 9824291]
[77]
Hong, M.; Zhukareva, V.; Vogelsberg-Ragaglia, V.; Wszolek, Z.; Reed, L.; Miller, B.I.; Geschwind, D.H.; Bird, T.D.; McKeel, D.; Goate, A.; Morris, J.C.; Wilhelmsen, K.C.; Schellenberg, G.D.; Trojanowski, J.Q.; Lee, V.M. Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17. Science, 1998, 282(5395), 1914-1917.
[http://dx.doi.org/10.1126/science.282.5395.1914] [PMID: 9836646]
[78]
Meyer, V.; Dinkel, P.D.; Luo, Y.; Yu, X.; Wei, G.; Zheng, J.; Eaton, G.R.; Ma, B.; Nussinov, R.; Eaton, S.S.; Margittai, M. Single mutations in tau modulate the populations of fibril conformers through seed selection. Angew. Chem. Int. Ed., 2014, 53(6), 1590-1593.
[http://dx.doi.org/10.1002/anie.201308473] [PMID: 24453187]
[79]
Strang, K.H.; Croft, C.L.; Sorrentino, Z.A.; Chakrabarty, P.; Golde, T.E.; Giasson, B.I. Distinct differences in prion-like seeding and aggregation between Tau protein variants provide mechanistic insights into tauopathies. J. Biol. Chem., 2018, 293(7), 2408-2421.
[http://dx.doi.org/10.1074/jbc.M117.815357] [PMID: 29259137]
[80]
Delisle, M.B.; Murrell, J.R.; Richardson, R.; Trofatter, J.A.; Rascol, O.; Soulages, X.; Mohr, M.; Calvas, P.; Ghetti, B. A mutation at codon 279 (N279K) in exon 10 of the Tau gene causes a tauopathy with dementia and supranuclear palsy. Acta Neuropathol., 1999, 98(1), 62-77.
[http://dx.doi.org/10.1007/s004010051052] [PMID: 10412802]
[81]
Hasegawa, M.; Smith, M.J.; Iijima, M.; Tabira, T.; Goedert, M. FTDP-17 mutations N279K and S305N in tau produce increased splicing of exon 10. FEBS Lett., 1999, 443(2), 93-96.
[http://dx.doi.org/10.1016/S0014-5793(98)01696-2] [PMID: 9989582]
[82]
Grazia Spillantini, M.; Yoshida, H.; Rizzini, C.; Lantos, P.L.; Khan, N.; Rossor, M.N.; Goedert, M.; Brown, J. A noveltau mutation (N296N) in familial dementia with swollen achromatic neurons and corticobasal inclusion bodies. Ann. Neurol., 2000, 48(6), 939-943.
[http://dx.doi.org/10.1002/1531-8249(200012)48:6<939::AID-ANA17>3.0.CO;2-1] [PMID: 11117553]
[83]
Iseki, E.; Matsumura, T.; Marui, W.; Hino, H.; Odawara, T.; Sugiyama, N.; Suzuki, K.; Sawada, H.; Arai, T.; Kosaka, K. Familial frontotemporal dementia and parkinsonism with a novel N296H mutation in exon 10 of the tau gene and a widespread tau accumulation in the glial cells. Acta Neuropathol., 2001, 102(3), 285-292.
[http://dx.doi.org/10.1007/s004010000333] [PMID: 11585254]
[84]
Deramecourt, V.; Lebert, F.; Maurage, C.A.; Fernandez-Gomez, F.J.; Dujardin, S.; Colin, M.; Sergeant, N.; Buée-Scherrer, V.; Clot, F.; Ber, I.L.; Brice, A.; Pasquier, F.; Buée, L. Clinical, neuropathological, and biochemical characterization of the novel tau mutation P332S. J. Alzheimers Dis., 2012, 31(4), 741-749.
[http://dx.doi.org/10.3233/JAD-2012-120160] [PMID: 22699846]
[85]
Jeganathan, S.; von Bergen, M.; Mandelkow, E.M.; Mandelkow, E. The natively unfolded character of tau and its aggregation to Alzheimer-like paired helical filaments. Biochemistry, 2008, 47(40), 10526-10539.
[http://dx.doi.org/10.1021/bi800783d] [PMID: 18783251]
[86]
Ramachandran, G.; Udgaonkar, J.B. Understanding the kinetic roles of the inducer heparin and of rod-like protofibrils during amyloid fibril formation by Tau protein. J. Biol. Chem., 2011, 286(45), 38948-38959.
[http://dx.doi.org/10.1074/jbc.M111.271874] [PMID: 21931162]
[87]
Sibille, N.; Sillen, A.; Leroy, A.; Wieruszeski, J.M.; Mulloy, B.; Landrieu, I.; Lippens, G. Structural impact of heparin binding to full-length Tau as studied by NMR spectroscopy. Biochemistry, 2006, 45(41), 12560-12572.
[http://dx.doi.org/10.1021/bi060964o] [PMID: 17029411]
[88]
Elbaum-Garfinkle, S.; Ramlall, T.; Rhoades, E. The role of the lipid bilayer in tau aggregation. Biophys. J., 2010, 98(11), 2722-2730.
[http://dx.doi.org/10.1016/j.bpj.2010.03.013] [PMID: 20513417]
[89]
Jones, E.M.; Dubey, M.; Camp, P.J.; Vernon, B.C.; Biernat, J.; Mandelkow, E.; Majewski, J.; Chi, E.Y. Interaction of tau protein with model lipid membranes induces tau structural compaction and membrane disruption. Biochemistry, 2012, 51(12), 2539-2550.
[http://dx.doi.org/10.1021/bi201857v] [PMID: 22401494]
[90]
Brandt, R.; Léger, J.; Lee, G. Interaction of tau with the neural plasma membrane mediated by tau’s amino-terminal projection domain. J. Cell Biol., 1995, 131(5), 1327-1340.
[http://dx.doi.org/10.1083/jcb.131.5.1327] [PMID: 8522593]
[91]
Künze, G.; Barré, P.; Scheidt, H.A.; Thomas, L.; Eliezer, D.; Huster, D. Binding of the three-repeat domain of tau to phospholipid membranes induces an aggregated-like state of the protein. Biochim. Biophys. Acta Biomembr., 2012, 1818(9), 2302-2313.
[http://dx.doi.org/10.1016/j.bbamem.2012.03.019] [PMID: 22521809]
[92]
Barré, P.; Eliezer, D. Structural transitions in tau k18 on micelle binding suggest a hierarchy in the efficacy of individual microtubule-binding repeats in filament nucleation. Protein Sci., 2013, 22(8), 1037-1048.
[http://dx.doi.org/10.1002/pro.2290] [PMID: 23740819]
[93]
Barré, P.; Eliezer, D. Folding of the repeat domain of tau upon binding to lipid surfaces. J. Mol. Biol., 2006, 362(2), 312-326.
[http://dx.doi.org/10.1016/j.jmb.2006.07.018] [PMID: 16908029]
[94]
Georgieva, E.R.; Xiao, S.; Borbat, P.P.; Freed, J.H.; Eliezer, D. Tau binds to lipid membrane surfaces via short amphipathic helices located in its microtubule-binding repeats. Biophys. J., 2014, 107(6), 1441-1452.
[http://dx.doi.org/10.1016/j.bpj.2014.07.046] [PMID: 25229151]
[95]
Fanni, A.M.; Vander Zanden, C.M.; Majewska, P.V.; Majewski, J.; Chi, E.Y. Membrane-mediated fibrillation and toxicity of the tau hexapeptide PHF6. J. Biol. Chem., 2019, 294(42), 15304-15317.
[http://dx.doi.org/10.1074/jbc.RA119.010003] [PMID: 31439664]
[96]
Majewski, J.; Jones, E.M.; Vander Zanden, C.M.; Biernat, J.; Mandelkow, E.; Chi, E.Y. Lipid membrane templated misfolding and self-assembly of intrinsically disordered tau protein. Sci. Rep., 2020, 10(1), 13324.
[http://dx.doi.org/10.1038/s41598-020-70208-6] [PMID: 32770092]
[97]
Smith, M.A.; Harris, P.L.R.; Sayre, L.M.; Perry, G. Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. Proc. Natl. Acad. Sci. USA, 1997, 94(18), 9866-9868.
[http://dx.doi.org/10.1073/pnas.94.18.9866] [PMID: 9275217]
[98]
Yamamoto, A.; Shin, R.W.; Hasegawa, K.; Naiki, H.; Sato, H.; Yoshimasu, F.; Kitamoto, T. Iron (III) induces aggregation of hyperphosphorylated τ and its reduction to iron (II) reverses the aggregation: implications in the formation of neurofibrillary tangles of Alzheimer’s disease. J. Neurochem., 2002, 82(5), 1137-1147.
[http://dx.doi.org/10.1046/j.1471-4159.2002.t01-1-01061.x] [PMID: 12358761]
[99]
Huang, Y.; Wu, Z.; Cao, Y.; Lang, M.; Lu, B.; Zhou, B. Zinc binding directly regulates tau toxicity independent of tau hyperphosphorylation. Cell Rep., 2014, 8(3), 831-842.
[http://dx.doi.org/10.1016/j.celrep.2014.06.047] [PMID: 25066125]
[100]
Li, X.; Du, X.; Ni, J. Zn2+ aggravates tau aggregation and neurotoxicity. Int. J. Mol. Sci., 2019, 20(3), 487.
[http://dx.doi.org/10.3390/ijms20030487] [PMID: 30678122]
[101]
Ahmadi, S.; Zhu, S.; Sharma, R.; Wu, B.; Soong, R.; Dutta Majumdar, R.; Wilson, D.J.; Simpson, A.J.; Kraatz, H.B. Aggregation of microtubule binding repeats of tau protein is promoted by Cu2+. ACS Omega, 2019, 4(3), 5356-5366.
[http://dx.doi.org/10.1021/acsomega.8b03595] [PMID: 31001602]
[102]
Roman, A.Y.; Devred, F.; Byrne, D.; La Rocca, R.; Ninkina, N.N.; Peyrot, V.; Tsvetkov, P.O. Zinc induces temperature-dependent reversible self-assembly of tau. J. Mol. Biol., 2019, 431(4), 687-695.
[http://dx.doi.org/10.1016/j.jmb.2018.12.008] [PMID: 30580037]
[103]
Ambadipudi, S.; Biernat, J.; Riedel, D.; Mandelkow, E.; Zweckstetter, M. Liquid–liquid phase separation of the microtubule-binding repeats of the Alzheimer-related protein Tau. Nat. Commun., 2017, 8(1), 275.
[http://dx.doi.org/10.1038/s41467-017-00480-0] [PMID: 28819146]
[104]
Wegmann, S.; Eftekharzadeh, B.; Tepper, K.; Zoltowska, K.M.; Bennett, R.E.; Dujardin, S.; Laskowski, P.R.; MacKenzie, D.; Kamath, T.; Commins, C.; Vanderburg, C.; Roe, A.D.; Fan, Z.; Molliex, A.M.; Hernandez-Vega, A.; Muller, D.; Hyman, A.A.; Mandelkow, E.; Taylor, J.P.; Hyman, B.T. Tau protein liquid–liquid phase separation can initiate tau aggregation. EMBO J., 2018, 37(7), e98049.
[http://dx.doi.org/10.15252/embj.201798049] [PMID: 29472250]
[105]
Nedelsky, N.B.; Taylor, J.P. Bridging biophysics and neurology: Aberrant phase transitions in neurodegenerative disease. Nat. Rev. Neurol., 2019, 15(5), 272-286.
[http://dx.doi.org/10.1038/s41582-019-0157-5] [PMID: 30890779]
[106]
Singh, V.; Xu, L.; Boyko, S.; Surewicz, K.; Surewicz, W.K. Zinc promotes liquid–liquid phase separation of tau protein. J. Biol. Chem., 2020, 295(18), 5850-5856.
[http://dx.doi.org/10.1074/jbc.AC120.013166] [PMID: 32229582]
[107]
Soto, C. Transmissible proteins: Expanding the prion heresy. Cell, 2012, 149(5), 968-977.
[http://dx.doi.org/10.1016/j.cell.2012.05.007] [PMID: 22632966]
[108]
Morales, R.; Estrada, L.D.; Diaz-Espinoza, R.; Morales-Scheihing, D.; Jara, M.C.; Castilla, J.; Soto, C. Molecular cross talk between misfolded proteins in animal models of Alzheimer’s and prion diseases. J. Neurosci., 2010, 30(13), 4528-4535.
[http://dx.doi.org/10.1523/JNEUROSCI.5924-09.2010] [PMID: 20357103]
[109]
Vasconcelos, B.; Stancu, I.C.; Buist, A.; Bird, M.; Wang, P.; Vanoosthuyse, A.; Van Kolen, K.; Verheyen, A.; Kienlen-Campard, P.; Octave, J.N.; Baatsen, P.; Moechars, D.; Dewachter, I. Heterotypic seeding of Tau fibrillization by pre-aggregated Abeta provides potent seeds for prion-like seeding and propagation of Tau-pathology in vivo. Acta Neuropathol., 2016, 131(4), 549-569.
[http://dx.doi.org/10.1007/s00401-015-1525-x] [PMID: 26739002]
[110]
Ferrari, A.; Hoerndli, F.; Baechi, T.; Nitsch, R.M.; Götz, J. β-Amyloid induces paired helical filament-like tau filaments in tissue culture. J. Biol. Chem., 2003, 278(41), 40162-40168.
[http://dx.doi.org/10.1074/jbc.M308243200] [PMID: 12893817]
[111]
Waxman, E.A.; Giasson, B.I. Induction of intracellular tau aggregation is promoted by α-synuclein seeds and provides novel insights into the hyperphosphorylation of tau. J. Neurosci., 2011, 31(21), 7604-7618.
[http://dx.doi.org/10.1523/JNEUROSCI.0297-11.2011] [PMID: 21613474]
[112]
Strodel, B. Amyloid aggregation simulations: challenges, advances and perspectives. Curr. Opin. Struct. Biol., 2021, 67, 145-152.
[http://dx.doi.org/10.1016/j.sbi.2020.10.019] [PMID: 33279865]
[113]
Itoh, S.G.; Okumura, H. All-atom molecular dynamics simulation methods for the aggregation of protein and peptides: replica exchange/permutation and nonequilibrium simulations. Methods Mol. Biol., 2022, 2340, 197-220.
[http://dx.doi.org/10.1007/978-1-0716-1546-1_10] [PMID: 35167076]
[114]
Dror, R.O.; Dirks, R.M.; Grossman, J.P.; Xu, H.; Shaw, D.E. Biomolecular simulation: A computational microscope for molecular biology. Annu. Rev. Biophys., 2012, 41(1), 429-452.
[http://dx.doi.org/10.1146/annurev-biophys-042910-155245] [PMID: 22577825]
[115]
Kästner, J. Umbrella sampling. Wiley Interdiscip. Rev. Comput. Mol. Sci., 2011, 1(6), 932-942.
[http://dx.doi.org/10.1002/wcms.66]
[116]
Sugita, Y.; Okamoto, Y. Replica-exchange molecular dynamics method for protein folding. Chem. Phys. Lett., 1999, 314(1-2), 141-151.
[http://dx.doi.org/10.1016/S0009-2614(99)01123-9]
[117]
Laio, A.; Gervasio, F.L. Metadynamics: a method to simulate rare events and reconstruct the free energy in biophysics, chemistry and material science. Rep. Prog. Phys., 2008, 71(12), 126601.
[http://dx.doi.org/10.1088/0034-4885/71/12/126601]
[118]
Zhou, R. Replica exchange molecular dynamics method for protein folding simulation. Methods Mol. Biol., 2007, 350, 205-223.
[PMID: 16957325]
[119]
Metropolis, N.; Rosenbluth, A.W.; Rosenbluth, M.N.; Teller, A.H.; Teller, E. Equation of state calculations by fast computing machines. J. Chem. Phys., 1953, 21(6), 1087-1092.
[http://dx.doi.org/10.1063/1.1699114]
[120]
Lu, S.; He, X.; Yang, Z.; Chai, Z.; Zhou, S.; Wang, J.; Rehman, A.U.; Ni, D.; Pu, J.; Sun, J.; Zhang, J. Activation pathway of a G protein-coupled receptor uncovers conformational intermediates as targets for allosteric drug design. Nat. Commun., 2021, 12(1), 4721.
[http://dx.doi.org/10.1038/s41467-021-25020-9] [PMID: 34354057]
[121]
Liu, H.; Li, Q.; Xiong, C.; Zhong, H.; Zhang, Q.; Liu, H.; Yao, X. Uncovering the effect of pS202/pT205/pS208 triple phosphorylations on the conformational features of the key fragment G192-T212 of tau protein. ACS Chem. Neurosci., 2021, 12(6), 1039-1048.
[http://dx.doi.org/10.1021/acschemneuro.1c00058] [PMID: 33663205]
[122]
Li, L.; Li, X.; Tang, Y.; Lao, Z.; Lei, J.; Wei, G. Common cancer mutations R175H and R273H drive the p53 DNA-binding domain towards aggregation-prone conformations. Phys. Chem. Chem. Phys., 2020, 22(17), 9225-9232.
[http://dx.doi.org/10.1039/C9CP06671C] [PMID: 32307496]
[123]
Song, D.; Wang, W.; Ye, W.; Ji, D.; Luo, R.; Chen, H.F. ff14IDPs force field improving the conformation sampling of intrinsically disordered proteins. Chem. Biol. Drug Des., 2017, 89(1), 5-15.
[http://dx.doi.org/10.1111/cbdd.12832] [PMID: 27484738]
[124]
Mu, J.; Liu, H.; Zhang, J.; Luo, R.; Chen, H.F. Recent force field strategies for intrinsically disordered proteins. J. Chem. Inf. Model., 2021, 61(3), 1037-1047.
[http://dx.doi.org/10.1021/acs.jcim.0c01175] [PMID: 33591749]
[125]
Smit, F.X.; Luiken, J.A.; Bolhuis, P.G. Primary fibril nucleation of aggregation prone tau fragments PHF6 and PHF6*. J. Phys. Chem. B, 2017, 121(15), 3250-3261.
[http://dx.doi.org/10.1021/acs.jpcb.6b07045] [PMID: 27776213]
[126]
Fichou, Y.; Schirò, G.; Gallat, F.X.; Laguri, C.; Moulin, M.; Combet, J.; Zamponi, M.; Härtlein, M.; Picart, C.; Mossou, E.; Lortat-Jacob, H.; Colletier, J.P.; Tobias, D.J.; Weik, M. Hydration water mobility is enhanced around tau amyloid fibers. Proc. Natl. Acad. Sci. USA, 2015, 112(20), 6365-6370.
[http://dx.doi.org/10.1073/pnas.1422824112] [PMID: 25918405]
[127]
Liu, H.; Zhong, H.; Liu, X.; Zhou, S.; Tan, S.; Liu, H.; Yao, X. Disclosing the mechanism of spontaneous aggregation and template-induced misfolding of the key hexapeptide (PHF6) of tau protein based on molecular dynamics simulation. ACS Chem. Neurosci., 2019, 10(12), 4810-4823.
[http://dx.doi.org/10.1021/acschemneuro.9b00488] [PMID: 31661961]
[128]
He, H.; Liu, Y.; Sun, Y.; Ding, F. Misfolding and self-assembly dynamics of microtubule-binding repeats of the Alzheimer-related protein tau. J. Chem. Inf. Model., 2021, 61(6), 2916-2925.
[http://dx.doi.org/10.1021/acs.jcim.1c00217] [PMID: 34032430]
[129]
Liu, H.; Liu, X.; Zhou, S.; An, X.; Liu, H.; Yao, X. Disclosing the template-induced misfolding mechanism of tau protein by studying the dissociation of the boundary chain from the formed tau fibril based on a steered molecular dynamics simulation. ACS Chem. Neurosci., 2019, 10(3), 1854-1865.
[http://dx.doi.org/10.1021/acschemneuro.8b00732] [PMID: 30665304]
[130]
Lyons, A.J.; Gandhi, N.S.; Mancera, R.L. Molecular dynamics simulation of the phosphorylation-induced conformational changes of a tau peptide fragment. Proteins, 2014, 82(9), 1907-1923.
[http://dx.doi.org/10.1002/prot.24544] [PMID: 24577753]
[131]
Gandhi, N.S.; Landrieu, I.; Byrne, C.; Kukic, P.; Amniai, L.; Cantrelle, F.X.; Wieruszeski, J.M.; Mancera, R.L.; Jacquot, Y.; Lippens, G. A phosphorylation-induced turn defines the Alzheimer’s disease AT8 antibody epitope on the tau protein. Angew. Chem. Int. Ed., 2015, 54(23), 6819-6823.
[http://dx.doi.org/10.1002/anie.201501898] [PMID: 25881502]
[132]
Shah, S.J.A.; Zhong, H.; Zhang, Q.; Liu, H. Deciphering the effect of lysine acetylation on the misfolding and aggregation of human tau fragment 171IPAKTPPAPK180 using molecular dynamic simulation and the Markov state model. Int. J. Mol. Sci., 2022, 23(5), 2399.
[http://dx.doi.org/10.3390/ijms23052399] [PMID: 35269542]
[133]
Zou, Y.; Guan, L. Unraveling the influence of K280 acetylation on the conformational features of tau core fragment: A molecular dynamics simulation study. Front. Mol. Biosci., 2021, 8, 801577.
[http://dx.doi.org/10.3389/fmolb.2021.801577] [PMID: 34966788]
[134]
Yuzwa, S.A.; Macauley, M.S.; Heinonen, J.E.; Shan, X.; Dennis, R.J.; He, Y.; Whitworth, G.E.; Stubbs, K.A.; McEachern, E.J.; Davies, G.J.; Vocadlo, D.J. A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo. Nat. Chem. Biol., 2008, 4(8), 483-490.
[http://dx.doi.org/10.1038/nchembio.96] [PMID: 18587388]
[135]
Brister, M.A.; Pandey, A.K.; Bielska, A.A.; Zondlo, N.J. OGlcNAcylation and phosphorylation have opposing structural effects in tau: Phosphothreonine induces particular conformational order. J. Am. Chem. Soc., 2014, 136(10), 3803-3816.
[http://dx.doi.org/10.1021/ja407156m] [PMID: 24559475]
[136]
Rani, L.; Mittal, J.; Mallajosyula, S.S. Effect of phosphorylation and O-GlcNAcylation on proline-rich domains of tau. J. Phys. Chem. B, 2020, 124(10), 1909-1918.
[http://dx.doi.org/10.1021/acs.jpcb.9b11720] [PMID: 32065850]
[137]
Larini, L.; Gessel, M.M.; LaPointe, N.E.; Do, T.D.; Bowers, M.T.; Feinstein, S.C.; Shea, J.E. Initiation of assembly of tau(273-284) and its ΔK280 mutant: an experimental and computational study. Phys. Chem. Chem. Phys., 2013, 15(23), 8916-8928.
[http://dx.doi.org/10.1039/c3cp00063j] [PMID: 23515417]
[138]
Raz, Y.; Adler, J.; Vogel, A.; Scheidt, H.A.; Häupl, T.; Abel, B.; Huster, D.; Miller, Y. The influence of the ΔK280 mutation and N- or C-terminal extensions on the structure, dynamics, and fibril morphology of the tau R2 repeat. Phys. Chem. Chem. Phys., 2014, 16(17), 7710-7717.
[http://dx.doi.org/10.1039/c3cp54890b] [PMID: 24448233]
[139]
Chen, D.; Drombosky, K.W.; Hou, Z.; Sari, L.; Kashmer, O.M.; Ryder, B.D.; Perez, V.A.; Woodard, D.R.; Lin, M.M.; Diamond, M.I.; Joachimiak, L.A. Tau local structure shields an amyloid-forming motif and controls aggregation propensity. Nat. Commun., 2019, 10(1), 2493.
[http://dx.doi.org/10.1038/s41467-019-10355-1] [PMID: 31175300]
[140]
Li, H.; Li, N.; Tang, Y.; Lee, J.Y. Histidine tautomeric effect on the key fragment R3 of tau protein from atomistic simulations. ACS Chem. Neurosci., 2021, 12(11), 1983-1988.
[http://dx.doi.org/10.1021/acschemneuro.1c00093] [PMID: 33978396]
[141]
Li, H.; Joo, E.; Lee, J.Y. Theoretical insights into mutation and histidine tautomerism effects on tau proteins. ACS Chem. Neurosci., 2021, 12(22), 4361-4366.
[http://dx.doi.org/10.1021/acschemneuro.1c00594] [PMID: 34735109]
[142]
Chatterjee, S.; Salimi, A.; Lee, J.Y. Molecular mechanism of amyloidogenicity and neurotoxicity of a pro-aggregated tau mutant in the presence of histidine tautomerism via replica-exchange simulation. Phys. Chem. Chem. Phys., 2021, 23(17), 10475-10486.
[http://dx.doi.org/10.1039/D1CP00105A] [PMID: 33899866]
[143]
Jing, J.; Tu, G.; Yu, H.; Huang, R.; Ming, X.; Zhan, H.; Zhan, F.; Xue, W. Copper (Cu 2+ ) ion-induced misfolding of tau protein R3 peptide revealed by enhanced molecular dynamics simulation. Phys. Chem. Chem. Phys., 2021, 23(20), 11717-11726.
[http://dx.doi.org/10.1039/D0CP05744D] [PMID: 33982037]
[144]
Dong, X.; Qi, R.; Qiao, Q.; Li, X.; Li, F.; Wan, J.; Zhang, Q.; Wei, G. Heparin remodels the microtubule-binding repeat R3 of Tau protein towards fibril-prone conformations. Phys. Chem. Chem. Phys., 2021, 23(36), 20406-20418.
[http://dx.doi.org/10.1039/D1CP02651H] [PMID: 34494046]
[145]
Chowdhury, U.D.; Paul, A.; Bhargava, B.L. The effect of lipid composition on the dynamics of tau fibrils. Proteins, 2022, 90(12), 2103-2115.
[http://dx.doi.org/10.1002/prot.26401] [PMID: 35869787]
[146]
Homeyer, N.; Horn, A.H.C.; Lanig, H.; Sticht, H. AMBER force-field parameters for phosphorylated amino acids in different protonation states: phosphoserine, phosphothreonine, phosphotyrosine, and phosphohistidine. J. Mol. Model., 2006, 12(3), 281-289.
[http://dx.doi.org/10.1007/s00894-005-0028-4] [PMID: 16240095]

Rights & Permissions Print Cite
Article Metrics
52
3
Wayfinder Image
World Antimicrobial Awareness Week
© 2024 Bentham Science Publishers | Privacy Policy