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Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Review Article

Post-Translational Modifications in Tau and Their Roles in Alzheimer's Pathology

Author(s): Subha Kalyaanamoorthy*, Stanley Kojo Opare, Xiaoxiao Xu, Aravindhan Ganesan and Praveen P.N. Rao

Volume 21, Issue 1, 2024

Published on: 15 April, 2024

Page: [24 - 49] Pages: 26

DOI: 10.2174/0115672050301407240408033046

Abstract

Microtubule-Associated Protein Tau (also known as tau) has been shown to accumulate into paired helical filaments and neurofibrillary tangles, which are known hallmarks of Alzheimer’s disease (AD) pathology. Decades of research have shown that tau protein undergoes extensive post-translational modifications (PTMs), which can alter the protein's structure, function, and dynamics and impact the various properties such as solubility, aggregation, localization, and homeostasis. There is a vast amount of information describing the impact and role of different PTMs in AD pathology and neuroprotection. However, the complex interplay between these PTMs remains elusive. Therefore, in this review, we aim to comprehend the key post-translational modifications occurring in tau and summarize potential connections to clarify their impact on the physiology and pathophysiology of tau. Further, we describe how different computational modeling methods have helped in understanding the impact of PTMs on the structure and functions of the tau protein. Finally, we highlight the tau PTM-related therapeutics strategies that are explored for the development of AD therapy.

Keywords: Alzheimer’s disease, tau protein, post-translational modifications, phosphorylation, acetylation, methylation, nitration, glycosylation, glycation, truncation, deamidation, ubiquitination, sumoylation, computational modeling, therapeutic approaches.

[1]
Jha, A.; Mukhopadhaya, K. Memory, cognitive impairment and dementia. In: Alzheimer’s Disease: Diagnosis and Treatment Guide; Springer International Publishing: Cham, 2021; pp. 1-20.
[http://dx.doi.org/10.1007/978-3-030-56739-2_1]
[2]
Matthews, K.A.; Xu, W.; Gaglioti, A.H.; Holt, J.B.; Croft, J.B.; Mack, D.; McGuire, L.C. Racial and ethnic estimates of Alzheimer’s disease and related dementias in the United States (2015–2060) in adults aged ≥65 years. Alzheimers Dement., 2019, 15(1), 17-24.
[http://dx.doi.org/10.1016/j.jalz.2018.06.3063] [PMID: 30243772]
[3]
Alzheimer’s disease and related dementias. 2020. Available from: https://www.cdc.gov/aging
[4]
Gauthier, S. World Alzheimer Report 2022: Life after diagnosis: Navigating treatment, care and support. In: World Alzheimer Reports; Benoist Chloe, W.W., Ed.; Alzheimer’s Disease International, 2022; p. 413.
[5]
Meyers, E.A.; Sexton, C.; Snyder, H.M.; Carrillo, M.C. Impact of Alzheimer’s association support and engagement in the AD/ADRD research community through the COVID-19 pandemic and beyond. Alzheimers Dement., 2023, 19(7), 3222-3225.
[http://dx.doi.org/10.1002/alz.13015] [PMID: 36872646]
[6]
Tay, L.X.; Ong, S.C.; Tay, L.J.; Ng, T.; Parumasivam, T. Economic burden of alzheimer’s disease: A systematic review. Value Health Reg. Issues, 2024, 40, 1-12.
[http://dx.doi.org/10.1016/j.vhri.2023.09.008] [PMID: 37972428]
[7]
Global action plan on the public health response to dementia 2017-2025. Ed.; World Health Organization. 2017
[8]
Achúcarro, N. Elongated and stäbechenzellen cells: Neuroglic cells and granulo-adipose cells at the Ammon horn of the rabbit; Nicolás Moya, 1909.
[9]
Achúcarro, N. Notes on the structure and functions of neuroglia and in particular of neuroglia of the human cerebral cortex; Children of Nicolás Moya, 1914.
[10]
Kim, S.R.; Lee, J.M. Prothrombin kringle-2, a mediator of microglial activation: new insight in Alzheimer’s disease pathogenesis. Neural Regen. Res., 2022, 17(12), 2675-2676.
[http://dx.doi.org/10.4103/1673-5374.335813] [PMID: 35662205]
[11]
Stelzmann, R.A.; Schnitzlein, H.N.; Murtagh, F.R.; Murtagh, F.R. An english translation of alzheimer’s 1907 paper, “über eine eigenartige erkankung der hirnrinde”. Clin. Anat., 1995, 8(6), 429-431.
[http://dx.doi.org/10.1002/ca.980080612] [PMID: 8713166]
[12]
Swerdlow, R.H.; Anderson, H.; Burns, J.M. Alzheimer’s disease. In: Encyclopedia of Clinical Neuropsychology; Kreutzer, J.S.; DeLuca, J.; Caplan, B., Eds.; Springer New York: New York, NY, 2011; pp. 105-110.
[http://dx.doi.org/10.1007/978-0-387-79948-3_290]
[13]
Mattson, M.P. Oxidative stress, perturbed calcium homeostasis, and immune dysfunction in Alzheimer’s disease. J. Neurovirol., 2002, 8(6), 539-550.
[http://dx.doi.org/10.1080/13550280290100978] [PMID: 12476348]
[14]
Cabezas, I.L.; Batista, A.H.; Rol, G.P. The role of glial cells in Alzheimer disease: Potential therapeutic implications. Neurologia, 2014, 29(5), 305-309.
[http://dx.doi.org/10.1016/j.nrl.2012.10.006] [PMID: 23246214]
[15]
Sahara, N.; Maeda, S.; Takashima, A. Tau oligomerization: A role for tau aggregation intermediates linked to neurodegeneration. Curr. Alzheimer Res., 2008, 5(6), 591-598.
[http://dx.doi.org/10.2174/156720508786898442] [PMID: 19075586]
[16]
Hosokawa, M.; Masuda-Suzukake, M.; Shitara, H.; Shimozawa, A.; Suzuki, G.; Kondo, H.; Nonaka, T.; Campbell, W.; Arai, T.; Hasegawa, M. Development of a novel tau propagation mouse model endogenously expressing 3 and 4 repeat tau isoforms. Brain, 2022, 145(1), 349-361.
[http://dx.doi.org/10.1093/brain/awab289] [PMID: 34515757]
[17]
Tsujikawa, K.; Hamanaka, K.; Riku, Y.; Hattori, Y.; Hara, N.; Iguchi, Y.; Ishigaki, S.; Hashizume, A.; Miyatake, S.; Mitsuhashi, S.; Miyazaki, Y.; Kataoka, M.; Jiayi, L.; Yasui, K.; Kuru, S.; Koike, H.; Kobayashi, K.; Sahara, N.; Ozaki, N.; Yoshida, M.; Kakita, A.; Saito, Y.; Iwasaki, Y.; Miyashita, A.; Iwatsubo, T.; Ikeuchi, T.; Miyata, T.; Sobue, G.; Matsumoto, N.; Sahashi, K.; Katsuno, M. Actin-binding protein filamin-A drives tau aggregation and contributes to progressive supranuclear palsy pathology. Sci. Adv., 2022, 8(21), eabm5029.
[http://dx.doi.org/10.1126/sciadv.abm5029] [PMID: 35613261]
[18]
Lukiw, W.J. Recent advances in our molecular and mechanistic understanding of misfolded cellular proteins in alzheimer’s disease (AD) and prion disease (PrD). Biomolecules, 2022, 12(2), 166.
[http://dx.doi.org/10.3390/biom12020166] [PMID: 35204666]
[19]
Petrozziello, T.; Bordt, E.A.; Mills, A.N.; Kim, S.E.; Sapp, E.; Devlin, B.A.; Obeng-Marnu, A.A.; Farhan, S.M.K.; Amaral, A.C.; Dujardin, S.; Dooley, P.M.; Henstridge, C.; Oakley, D.H.; Neueder, A.; Hyman, B.T.; Spires-Jones, T.L.; Bilbo, S.D.; Vakili, K.; Cudkowicz, M.E.; Berry, J.D.; DiFiglia, M.; Silva, M.C.; Haggarty, S.J.; Sadri-Vakili, G. Targeting tau mitigates mitochondrial fragmentation and oxidative stress in amyotrophic lateral sclerosis. Mol. Neurobiol., 2022, 59(1), 683-702.
[http://dx.doi.org/10.1007/s12035-021-02557-w] [PMID: 34757590]
[20]
Liang, S.Y.; Wang, Z.T.; Tan, L.; Yu, J.T. Tau toxicity in neurodegeneration. Mol. Neurobiol., 2022, 59(6), 3617-3634.
[http://dx.doi.org/10.1007/s12035-022-02809-3] [PMID: 35359226]
[21]
Maeda, S.; Sahara, N.; Saito, Y.; Murayama, M.; Yoshiike, Y.; Kim, H.; Miyasaka, T.; Murayama, S.; Ikai, A.; Takashima, A. Granular tau oligomers as intermediates of tau filaments. Biochemistry, 2007, 46(12), 3856-3861.
[http://dx.doi.org/10.1021/bi061359o] [PMID: 17338548]
[22]
Gerson, J.E.; Sengupta, U.; Lasagna-Reeves, C.A.; Guerrero- Muñoz, M.J.; Troncoso, J.; Kayed, R. Characterization of tau oligomeric seeds in progressive supranuclear palsy. Acta Neuropathol. Commun., 2014, 2(1), 73.
[http://dx.doi.org/10.1186/2051-5960-2-73] [PMID: 24927818]
[23]
Shafiei, S.S.; Guerrero-Muñoz, M.J.; Castillo-Carranza, D.L. Tau oligomers: Cytotoxicity, propagation, and mitochondrial damage. Front. Aging Neurosci., 2017, 9, 83.
[http://dx.doi.org/10.3389/fnagi.2017.00083] [PMID: 28420982]
[24]
Peeraer, E.; Bottelbergs, A.; van Kolen, K.; Stancu, I.C.; Vasconcelos, B.; Mahieu, M.; Duytschaever, H.; Ver Donck, L.; Torremans, A.; Sluydts, E.; Van Acker, N.; Kemp, J.A.; Mercken, M.; Brunden, K.R.; Trojanowski, J.Q.; Dewachter, I.; Lee, V.M.Y.; Moechars, D. Intracerebral injection of preformed synthetic tau fibrils initiates widespread tauopathy and neuronal loss in the brains of tau transgenic mice. Neurobiol. Dis., 2015, 73, 83-95.
[http://dx.doi.org/10.1016/j.nbd.2014.08.032] [PMID: 25220759]
[25]
Alquezar, C.; Arya, S.; Kao, A.W. Tau post-translational modifications: Dynamic transformers of tau function, degradation, and aggregation. Front. Neurol., 2021, 11, 595532.
[http://dx.doi.org/10.3389/fneur.2020.595532] [PMID: 33488497]
[26]
Marcelli, S.; Corbo, M.; Iannuzzi, F.; Negri, L.; Blandini, F.; Nistico, R.; Feligioni, M. The involvement of post-translational modifications in alzheimer’s disease. Curr. Alzheimer Res., 2018, 15(4), 313-335.
[http://dx.doi.org/10.2174/1567205014666170505095109] [PMID: 28474569]
[27]
Selkoe, D.J. The therapeutics of Alzheimer’s disease: Where we stand and where we are heading. Ann. Neurol., 2013, 74(3), 328-336.
[http://dx.doi.org/10.1002/ana.24001] [PMID: 25813842]
[28]
Ashraf, G.; Greig, N.; Khan, T.; Hassan, I.; Tabrez, S.; Shakil, S.; Sheikh, I.; Zaidi, S.; Akram, M.; Jabir, N.; Firoz, C.; Naeem, A.; Alhazza, I.; Damanhouri, G.; Kamal, M. Protein misfolding and aggregation in Alzheimer’s disease and type 2 diabetes mellitus. CNS Neurol. Disord. Drug Targets, 2014, 13(7), 1280-1293.
[http://dx.doi.org/10.2174/1871527313666140917095514] [PMID: 25230234]
[29]
Braak, H.; Braak, E. Staging of alzheimer’s disease-related neurofibrillary changes. Neurobiol. Aging, 1995, 16(3), 271-278.
[http://dx.doi.org/10.1016/0197-4580(95)00021-6] [PMID: 7566337]
[30]
Iqbal, K.; Novak, M. From tangles to tau protein. Bratisl. Lek Listy, 2006, 107(9-10), 341-342.
[PMID: 17262984]
[31]
Fuentes, P.; Catalan, J. A clinical perspective: Anti tau’s treatment in Alzheimer’s disease. Curr. Alzheimer Res., 2011, 8(6), 686-688.
[http://dx.doi.org/10.2174/156720511796717221] [PMID: 21605037]
[32]
Ceyzériat, K.; Zilli, T.; Millet, P.; Frisoni, G.B.; Garibotto, V.; Tournier, B.B. Learning from the past: A review of clinical trials targeting amyloid, tau and neuroinflammation in alzheimer’s disease. Curr. Alzheimer Res., 2020, 17(2), 112-125.
[http://dx.doi.org/10.2174/1567205017666200304085513] [PMID: 32129164]
[33]
Cook, C.; Stankowski, J.N.; Carlomagno, Y.; Stetler, C.; Petrucelli, L. Acetylation: A new key to unlock tau’s role in neurodegeneration. Alzheimers Res. Ther., 2014, 6(3), 29.
[http://dx.doi.org/10.1186/alzrt259] [PMID: 25031639]
[34]
Wegmann, S.; Biernat, J.; Mandelkow, E. A current view on Tau protein phosphorylation in Alzheimer’s disease. Curr. Opin. Neurobiol., 2021, 69, 131-138.
[http://dx.doi.org/10.1016/j.conb.2021.03.003] [PMID: 33892381]
[35]
Park, S.; Lee, J.H.; Jeon, J.H.; Lee, M.J. Degradation or aggregation: The ramifications of post-translational modifications on tau. BMB Rep., 2018, 51(6), 265-273.
[http://dx.doi.org/10.5483/BMBRep.2018.51.6.077] [PMID: 29661268]
[36]
Reily, C.; Stewart, T.J.; Renfrow, M.B.; Novak, J. Glycosylation in health and disease. Nat. Rev. Nephrol., 2019, 15(6), 346-366.
[http://dx.doi.org/10.1038/s41581-019-0129-4] [PMID: 30858582]
[37]
Morishima-Kawashima, M.; Hasegawa, M.; Takio, K.; Suzuki, M.; Yoshida, H.; Watanabe, A.; Titani, K.; Ihara, Y. Hyperphosphorylation of Tau in PHF. Neurobiol. Aging, 1995, 16(3), 365-371.
[http://dx.doi.org/10.1016/0197-4580(95)00027-C] [PMID: 7566346]
[38]
Haukedal, H.; Freude, K.K. Implications of glycosylation in alzheimer’s disease. Front. Neurosci., 2021, 14, 625348.
[http://dx.doi.org/10.3389/fnins.2020.625348] [PMID: 33519371]
[39]
Yang, X.J.; Seto, E. Lysine acetylation: Codified crosstalk with other posttranslational modifications. Mol. Cell, 2008, 31(4), 449-461.
[http://dx.doi.org/10.1016/j.molcel.2008.07.002] [PMID: 18722172]
[40]
Funk, K.E.; Thomas, S.N.; Schafer, K.N.; Cooper, G.L.; Liao, Z.; Clark, D.J.; Yang, A.J.; Kuret, J. Lysine methylation is an endogenous post-translational modification of tau protein in human brain and a modulator of aggregation propensity. Biochem. J., 2014, 462(1), 77-88.
[http://dx.doi.org/10.1042/BJ20140372] [PMID: 24869773]
[41]
Gong, C.X.; Liu, F.; Iqbal, K. O-GlcNAcylation: A regulator of tau pathology and neurodegeneration. Alzheimers Dement., 2016, 12(10), 1078-1089.
[http://dx.doi.org/10.1016/j.jalz.2016.02.011] [PMID: 27126545]
[42]
Mondragón-Rodríguez, S. Phosphorylation of tau protein as the link between oxidative stress, mitochondrial dysfunction, and connectivity failure: Implications for Alzheimer’s disease. Oxid Med Cell Longev., 2013, 2013, 940603.
[http://dx.doi.org/10.1155/2013/940603]
[43]
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]
[44]
Liu, F.; Zaidi, T.; Iqbal, K.; Grundke-Iqbal, I.; Merkle, R.K.; Gong, C.X. Role of glycosylation in hyperphosphorylation of tau in Alzheimer’s disease. FEBS Lett., 2002, 512(1-3), 101-106.
[http://dx.doi.org/10.1016/S0014-5793(02)02228-7] [PMID: 11852060]
[45]
Ye, H.; Han, Y.; Li, P.; Su, Z.; Huang, Y. The role of post-translational modifications on the structure and function of tau protein. J. Mol. Neurosci., 2022, 72(8), 1557-1571.
[http://dx.doi.org/10.1007/s12031-022-02002-0] [PMID: 35325356]
[46]
Mandel, N.; Agarwal, N. Role of SUMOylation in neurodegenerative diseases. Cells, 2022, 11(21), 3395.
[http://dx.doi.org/10.3390/cells11213395] [PMID: 36359791]
[47]
Sarge, K.D.; Park-Sarge, O.K. SUMOylation and human disease pathogenesis. Trends Biochem. Sci., 2009, 34(4), 200-205.
[http://dx.doi.org/10.1016/j.tibs.2009.01.004] [PMID: 19282183]
[48]
Stoothoff, W.H.; Johnson, G.V.W. Tau phosphorylation: Physiological and pathological consequences. Biochim. Biophys. Acta Mol. Basis Dis., 2005, 1739(2-3), 280-297.
[http://dx.doi.org/10.1016/j.bbadis.2004.06.017] [PMID: 15615646]
[49]
Morris, M.; Knudsen, G.M.; Maeda, S.; Trinidad, J.C.; Ioanoviciu, A.; Burlingame, A.L.; Mucke, L. Tau post-translational modifications in wild-type and human amyloid precursor protein transgenic mice. Nat. Neurosci., 2015, 18(8), 1183-1189.
[http://dx.doi.org/10.1038/nn.4067] [PMID: 26192747]
[50]
Guillozet-Bongaarts, A.L.; Garcia-Sierra, F.; Reynolds, M.R.; Horowitz, P.M.; Fu, Y.; Wang, T.; Cahill, M.E.; Bigio, E.H.; Berry, R.W.; Binder, L.I. Tau truncation during neurofibrillary tangle evolution in Alzheimer’s disease. Neurobiol. Aging, 2005, 26(7), 1015-1022.
[http://dx.doi.org/10.1016/j.neurobiolaging.2004.09.019] [PMID: 15748781]
[51]
Li, L.; Jiang, Y.; Wang, J.Z.; Liu, R.; Wang, X. Tau ubiquitination in alzheimer’s disease. Front. Neurol., 2022, 12, 786353.
[http://dx.doi.org/10.3389/fneur.2021.786353] [PMID: 35211074]
[52]
Oliveira, J.; Costa, M.; de Almeida, M.S.C.; da Cruz e Silva, O.A.B.; Henriques, A.G. Protein phosphorylation is a key mechanism in Alzheimer’s disease. J. Alzheimers Dis., 2017, 58(4), 953-978.
[http://dx.doi.org/10.3233/JAD-170176] [PMID: 28527217]
[53]
Tolnay, M.; Sergeant, N.; Ghestem, A.; Chalbot, S.; de Vos, R.A.; Jansen Steur, E.N.; Probst, A.; Delacourte, A. Argyrophilic grain disease and Alzheimer’s disease are distinguished by their different distribution of tau protein isoforms. Acta Neuropathol., 2002, 104(4), 425-434.
[http://dx.doi.org/10.1007/s00401-002-0591-z] [PMID: 12200631]
[54]
Drepper, F.; Biernat, J.; Kaniyappan, S.; Meyer, H.E.; Mandelkow, E.M.; Warscheid, B.; Mandelkow, E. A combinatorial native MS and LC-MS/MS approach reveals high intrinsic phosphorylation of human Tau but minimal levels of other key modifications. J. Biol. Chem., 2020, 295(52), 18213-18225.
[http://dx.doi.org/10.1074/jbc.RA120.015882] [PMID: 33106314]
[55]
Kimura, T.; Sharma, G.; Ishiguro, K.; Hisanaga, S. Phospho-tau bar code: Analysis of phosphoisotypes of tau and its application to tauopathy. Front. Neurosci., 2018, 12, 44.
[http://dx.doi.org/10.3389/fnins.2018.00044] [PMID: 29467609]
[56]
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]
[57]
Buée, L.; Bussière, T.; Buée-Scherrer, V.; Delacourte, A.; Hof, P.R. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res. Brain Res. Rev., 2000, 33(1), 95-130.
[http://dx.doi.org/10.1016/S0165-0173(00)00019-9] [PMID: 10967355]
[58]
Haj-Yahya, M. Site-specific hyperphosphorylation of tau inhibits its fibrillization in vitro, blocks its seeding capacity in cells, and disrupts its microtubule binding; Implications for the native state stabilization of tau. bioRxiv, 2019, 772046.
[http://dx.doi.org/10.1101/772046]
[59]
Zhou, X.W.; Li, X.; Bjorkdahl, C.; Sjogren, M.J.; Alafuzoff, I.; Soininen, H.; Grundke-Iqbal, I.; Iqbal, K.; Winblad, B.; Pei, J.J. Assessments of the accumulation severities of amyloid β-protein and hyperphosphorylated tau in the medial temporal cortex of control and Alzheimer’s brains. Neurobiol. Dis., 2006, 22(3), 657-668.
[http://dx.doi.org/10.1016/j.nbd.2006.01.006] [PMID: 16513361]
[60]
Šimić, G.; Babić Leko, M.; Wray, S.; Harrington, C.; Delalle, I.; Jovanov-Milošević, N.; Bažadona, D.; Buée, L.; de Silva, R.; Di Giovanni, G.; Wischik, C.; Hof, P. Tau protein hyperphosphorylation and aggregation in Alzheimer’s disease and other tauopathies, and possible neuroprotective strategies. Biomolecules, 2016, 6(1), 6.
[http://dx.doi.org/10.3390/biom6010006] [PMID: 26751493]
[61]
Su, J.H.; Cummings, B.J.; Cotman, C.W. Early phosphorylation of tau in Alzheimerʼs disease occurs at Ser-202 and is preferentially located within neurites. Neuroreport, 1994, 5(17), 2358-2362.
[http://dx.doi.org/10.1097/00001756-199411000-00037] [PMID: 7533559]
[62]
Iqbal, K.; Grundke-Iqbal, I. Ubiquitination and abnormal phosphorylation of paired helical filaments in Alzheimer’s disease. Mol. Neurobiol., 1991, 5(2-4), 399-410.
[http://dx.doi.org/10.1007/BF02935561] [PMID: 1726645]
[63]
Guillozet-Bongaarts, A.L.; Cahill, M.E.; Cryns, V.L.; Reynolds, M.R.; Berry, R.W.; Binder, L.I. Pseudophosphorylation of tau at serine 422 inhibits caspase cleavage: In vitro evidence and implications for tangle formation in vivo. J. Neurochem., 2006, 97(4), 1005-1014.
[http://dx.doi.org/10.1111/j.1471-4159.2006.03784.x] [PMID: 16606369]
[64]
Dickey, C.A.; Kamal, A.; Lundgren, K.; Klosak, N.; Bailey, R.M.; Dunmore, J.; Ash, P.; Shoraka, S.; Zlatkovic, J.; Eckman, C.B.; Patterson, C.; Dickson, D.W.; Nahman, N.S., Jr; Hutton, M.; Burrows, F.; Petrucelli, L. The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins. J. Clin. Invest., 2007, 117(3), 648-658.
[http://dx.doi.org/10.1172/JCI29715] [PMID: 17304350]
[65]
Hoover, B.R.; Reed, M.N.; Su, J.; Penrod, R.D.; Kotilinek, L.A.; Grant, M.K.; Pitstick, R.; Carlson, G.A.; Lanier, L.M.; Yuan, L.L.; Ashe, K.H.; Liao, D. Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration. Neuron, 2010, 68(6), 1067-1081.
[http://dx.doi.org/10.1016/j.neuron.2010.11.030] [PMID: 21172610]
[66]
Lu, P.J.; Wulf, G.; Zhou, X.Z.; Davies, P.; Lu, K.P. The prolyl isomerase Pin1 restores the function of Alzheimer-associated phosphorylated tau protein. Nature, 1999, 399(6738), 784-788.
[http://dx.doi.org/10.1038/21650] [PMID: 10391244]
[67]
Kondo, A.; Shahpasand, K.; Mannix, R.; Qiu, J.; Moncaster, J.; Chen, C.H.; Yao, Y.; Lin, Y.M.; Driver, J.A.; Sun, Y.; Wei, S.; Luo, M.L.; Albayram, O.; Huang, P.; Rotenberg, A.; Ryo, A.; Goldstein, L.E.; Pascual-Leone, A.; McKee, A.C.; Meehan, W.; Zhou, X.Z.; Lu, K.P. Antibody against early driver of neurodegeneration cis P-tau blocks brain injury and tauopathy. Nature, 2015, 523(7561), 431-436.
[http://dx.doi.org/10.1038/nature14658] [PMID: 26176913]
[68]
Lee, T.H.; Chen, C.H.; Suizu, F.; Huang, P.; Schiene-Fischer, C.; Daum, S.; Zhang, Y.J.; Goate, A.; Chen, R.H.; Zhou, X.Z.; Lu, K.P. Death-associated protein kinase 1 phosphorylates Pin1 and inhibits its prolyl isomerase activity and cellular function. Mol. Cell, 2011, 42(2), 147-159.
[http://dx.doi.org/10.1016/j.molcel.2011.03.005] [PMID: 21497122]
[69]
Balastik, M.; Lim, J.; Pastorino, L.; Lu, K.P. Pin1 in Alzheimer’s disease: Multiple substrates, one regulatory mechanism? Biochim. Biophys. Acta Mol. Basis Dis., 2007, 1772(4), 422-429.
[http://dx.doi.org/10.1016/j.bbadis.2007.01.006] [PMID: 17317113]
[70]
Buerger, K.; Ewers, M.; Pirttilä, T.; Zinkowski, R.; Alafuzoff, I.; Teipel, S.J.; DeBernardis, J.; Kerkman, D.; McCulloch, C.; Soininen, H.; Hampel, H. CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer’s disease. Brain, 2006, 129(11), 3035-3041.
[http://dx.doi.org/10.1093/brain/awl269] [PMID: 17012293]
[71]
Gong, C.X.; Singh, T.J.; Grundke-Iqbal, I.; Iqbal, K. Phosphoprotein phosphatase activities in Alzheimer disease brain. J. Neurochem., 1993, 61(3), 921-927.
[http://dx.doi.org/10.1111/j.1471-4159.1993.tb03603.x] [PMID: 8395566]
[72]
Chen, S.; Li, B.; Grundke-Iqbal, I.; Iqbal, K. I1PP2A affects tau phosphorylation via association with the catalytic subunit of protein phosphatase 2A. J. Biol. Chem., 2008, 283(16), 10513-10521.
[http://dx.doi.org/10.1074/jbc.M709852200] [PMID: 18245083]
[73]
Hart, G.W.; Slawson, C.; Ramirez-Correa, G.; Lagerlof, O. Cross talk between O-GlcNAcylation and phosphorylation: Roles in signaling, transcription, and chronic disease. Annu. Rev. Biochem., 2011, 80(1), 825-858.
[http://dx.doi.org/10.1146/annurev-biochem-060608-102511] [PMID: 21391816]
[74]
Liu, F.; Iqbal, K.; Grundke-Iqbal, I.; Hart, G.W.; Gong, C.X. O-GlcNAcylation regulates phosphorylation of tau: A mechanism involved in Alzheimer’s disease. Proc. Natl. Acad. Sci. USA, 2004, 101(29), 10804-10809.
[http://dx.doi.org/10.1073/pnas.0400348101] [PMID: 15249677]
[75]
O’Donnell, N.; Zachara, N.E.; Hart, G.W.; Marth, J.D. Ogt-dependent X-chromosome-linked protein glycosylation is a requisite modification in somatic cell function and embryo viability. Mol. Cell. Biol., 2004, 24(4), 1680-1690.
[http://dx.doi.org/10.1128/MCB.24.4.1680-1690.2004] [PMID: 14749383]
[76]
Soeda, Y.; Takashima, A. New insights into drug discovery targeting tau protein. Front. Mol. Neurosci., 2020, 13, 590896.
[http://dx.doi.org/10.3389/fnmol.2020.590896] [PMID: 33343298]
[77]
Carlomagno, Y.; Chung, D.C.; Yue, M.; Castanedes-Casey, M.; Madden, B.J.; Dunmore, J.; Tong, J.; DeTure, M.; Dickson, D.W.; Petrucelli, L.; Cook, C. An acetylation–phosphorylation switch that regulates tau aggregation propensity and function. J. Biol. Chem., 2017, 292(37), 15277-15286.
[http://dx.doi.org/10.1074/jbc.M117.794602] [PMID: 28760828]
[78]
Xia, Y.; Bell, B.M.; Giasson, B.I. Tau K321/K353 pseudoacetylation within KXGS motifs regulates tau–microtubule interactions and inhibits aggregation. Sci. Rep., 2021, 11(1), 17069.
[http://dx.doi.org/10.1038/s41598-021-96627-7] [PMID: 34426645]
[79]
Julien, C.; Tremblay, C.; Émond, V.; Lebbadi, M.; Salem, N., Jr; Bennett, D.A.; Calon, F. Sirtuin 1 reduction parallels the accumulation of tau in Alzheimer disease. J. Neuropathol. Exp. Neurol., 2009, 68(1), 48-58.
[http://dx.doi.org/10.1097/NEN.0b013e3181922348] [PMID: 19104446]
[80]
Min, S.W.; Cho, S.H.; Zhou, Y.; Schroeder, S.; Haroutunian, V.; Seeley, W.W.; Huang, E.J.; Shen, Y.; Masliah, E.; Mukherjee, C.; Meyers, D.; Cole, P.A.; Ott, M.; Gan, L. Acetylation of tau inhibits its degradation and contributes to tauopathy. Neuron, 2010, 67(6), 953-966.
[http://dx.doi.org/10.1016/j.neuron.2010.08.044] [PMID: 20869593]
[81]
Gorsky, M.K.; Burnouf, S.; Dols, J.; Mandelkow, E.; Partridge, L. Acetylation mimic of lysine 280 exacerbates human Tau neurotoxicity in vivo. Sci. Rep., 2016, 6(1), 22685.
[http://dx.doi.org/10.1038/srep22685] [PMID: 26940749]
[82]
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]
[83]
Min, S.W.; Chen, X.; Tracy, T.E.; Li, Y.; Zhou, Y.; Wang, C.; Shirakawa, K.; Minami, S.S.; Defensor, E.; Mok, S.A.; Sohn, P.D.; Schilling, B.; Cong, X.; Ellerby, L.; Gibson, B.W.; Johnson, J.; Krogan, N.; Shamloo, M.; Gestwicki, J.; Masliah, E.; Verdin, E.; Gan, L. Critical role of acetylation in tau-mediated neurodegeneration and cognitive deficits. Nat. Med., 2015, 21(10), 1154-1162.
[http://dx.doi.org/10.1038/nm.3951] [PMID: 26390242]
[84]
Boulton, T.G.; Yancopoulos, G.D.; Gregory, J.S.; Slaughter, C.; Moomaw, C.; Hsu, J.; Cobb, M.H. An insulin-stimulated protein kinase similar to yeast kinases involved in cell cycle control. Science, 1990, 249(4964), 64-67.
[http://dx.doi.org/10.1126/science.2164259] [PMID: 2164259]
[85]
Cohen, T.J.; Friedmann, D.; Hwang, A.W.; Marmorstein, R.; Lee, V.M.Y. The microtubule-associated tau protein has intrinsic acetyltransferase activity. Nat. Struct. Mol. Biol., 2013, 20(6), 756-762.
[http://dx.doi.org/10.1038/nsmb.2555] [PMID: 23624859]
[86]
Cohen, T.J.; Constance, B.H.; Hwang, A.W.; James, M.; Yuan, C.X. Intrinsic tau acetylation is coupled to auto-proteolytic tau fragmentation. PLoS One, 2016, 11(7), e0158470.
[http://dx.doi.org/10.1371/journal.pone.0158470] [PMID: 27383765]
[87]
Luo, Y.; Ma, B.; Nussinov, R.; Wei, G. Structural insight into tau protein’s paradox of intrinsically disordered behavior, self-acetylation activity, and aggregation. J. Phys. Chem. Lett., 2014, 5(17), 3026-3031.
[http://dx.doi.org/10.1021/jz501457f] [PMID: 25206938]
[88]
Sohn, P.D.; Tracy, T.E.; Son, H.I.; Zhou, Y.; Leite, R.E.P.; Miller, B.L.; Seeley, W.W.; Grinberg, L.T.; Gan, L. Acetylated tau destabilizes the cytoskeleton in the axon initial segment and is mislocalized to the somatodendritic compartment. Mol. Neurodegener., 2016, 11(1), 47.
[http://dx.doi.org/10.1186/s13024-016-0109-0] [PMID: 27356871]
[89]
Cook, C.; Carlomagno, Y.; Gendron, T.F.; Dunmore, J.; Scheffel, K.; Stetler, C.; Davis, M.; Dickson, D.; Jarpe, M.; DeTure, M.; Petrucelli, L. Acetylation of the KXGS motifs in tau is a critical determinant in modulation of tau aggregation and clearance. Hum. Mol. Genet., 2014, 23(1), 104-116.
[http://dx.doi.org/10.1093/hmg/ddt402] [PMID: 23962722]
[90]
Yao, Z.; Gao, M.; Huang, Y. Acetylation of lysine residues within the MT-binding repeats specifically modulates the structure ensemble of Tau. FASEB J., 2018, 32(S1), lb34-lb34.
[http://dx.doi.org/10.1096/fasebj.2018.32.1_supplement.lb34]
[91]
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]
[92]
Balmik, A.A.; Chinnathambi, S. Methylation as a key regulator of Tau aggregation and neuronal health in Alzheimer’s disease. Cell Commun. Signal., 2021, 19(1), 51.
[http://dx.doi.org/10.1186/s12964-021-00732-z] [PMID: 33962636]
[93]
Kontaxi, C.; Piccardo, P.; Gill, A.C. Lysine-directed post-translational modifications of tau protein in Alzheimer’s disease and related tauopathies. Front. Mol. Biosci., 2017, 4, 56.
[http://dx.doi.org/10.3389/fmolb.2017.00056] [PMID: 28848737]
[94]
Shams, H.; Matsunaga, A.; Ma, Q.; Mofrad, M.R.K.; Didonna, A. Methylation at a conserved lysine residue modulates tau assembly and cellular functions. Mol. Cell. Neurosci., 2022, 120, 103707.
[http://dx.doi.org/10.1016/j.mcn.2022.103707] [PMID: 35231567]
[95]
Bichmann, M.; Prat Oriol, N.; Ercan-Herbst, E.; Schöndorf, D.C.; Gomez Ramos, B.; Schwärzler, V.; Neu, M.; Schlüter, A.; Wang, X.; Jin, L.; Hu, C.; Tian, Y.; Ried, J.S.; Haberkant, P.; Gasparini, L.; Ehrnhoefer, D.E. SETD7-mediated monomethylation is enriched on soluble Tau in Alzheimer’s disease. Mol. Neurodegener., 2021, 16(1), 46.
[http://dx.doi.org/10.1186/s13024-021-00468-x] [PMID: 34215303]
[96]
Wang, P.; Joberty, G.; Buist, A.; Vanoosthuyse, A.; Stancu, I.C.; Vasconcelos, B.; Pierrot, N.; Faelth-Savitski, M.; Kienlen-Campard, P.; Octave, J.N.; Bantscheff, M.; Drewes, G.; Moechars, D.; Dewachter, I. Tau interactome mapping based identification of Otub1 as Tau deubiquitinase involved in accumulation of pathological Tau forms in vitro and in vivo. Acta Neuropathol., 2017, 133(5), 731-749.
[http://dx.doi.org/10.1007/s00401-016-1663-9] [PMID: 28083634]
[97]
Xu, Z.; Kohli, E.; Devlin, K.I.; Bold, M.; Nix, J.C.; Misra, S. Interactions between the quality control ubiquitin ligase CHIP and ubiquitin conjugating enzymes. BMC Struct. Biol., 2008, 8(1), 26.
[http://dx.doi.org/10.1186/1472-6807-8-26] [PMID: 18485199]
[98]
Petrucelli, L.; Dickson, D.; Kehoe, K.; Taylor, J.; Snyder, H.; Grover, A.; De Lucia, M.; McGowan, E.; Lewis, J.; Prihar, G.; Kim, J.; Dillmann, W.H.; Browne, S.E.; Hall, A.; Voellmy, R.; Tsuboi, Y.; Dawson, T.M.; Wolozin, B.; Hardy, J.; Hutton, M. CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation. Hum. Mol. Genet., 2004, 13(7), 703-714.
[http://dx.doi.org/10.1093/hmg/ddh083] [PMID: 14962978]
[99]
Flach, K.; Ramminger, E.; Hilbrich, I.; Arsalan-Werner, A.; Albrecht, F.; Herrmann, L.; Goedert, M.; Arendt, T.; Holzer, M. Axotrophin/MARCH7 acts as an E3 ubiquitin ligase and ubiquitinates tau protein in vitro impairing microtubule binding. Biochim. Biophys. Acta Mol. Basis Dis., 2014, 1842(9), 1527-1538.
[http://dx.doi.org/10.1016/j.bbadis.2014.05.029] [PMID: 24905733]
[100]
Babu, J.R.; Geetha, T.; Wooten, M.W. Sequestosome 1/p62 shuttles polyubiquitinated tau for proteasomal degradation. J. Neurochem., 2005, 94(1), 192-203.
[http://dx.doi.org/10.1111/j.1471-4159.2005.03181.x] [PMID: 15953362]
[101]
Cripps, D.; Thomas, S.N.; Jeng, Y.; Yang, F.; Davies, P.; Yang, A.J. 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., 2006, 281(16), 10825-10838.
[http://dx.doi.org/10.1074/jbc.M512786200] [PMID: 16443603]
[102]
Morishima-Kawashima, M.; Hasegawa, M.; Takio, K.; Suzuki, M.; Titani, K.; Ihara, Y. Ubiquitin is conjugated with amino-terminally processed tau in paired helical filaments. Neuron, 1993, 10(6), 1151-1160.
[http://dx.doi.org/10.1016/0896-6273(93)90063-W] [PMID: 8391280]
[103]
Dolan, P.J.; Johnson, G.V.W. A caspase cleaved form of tau is preferentially degraded through the autophagy pathway. J. Biol. Chem., 2010, 285(29), 21978-21987.
[http://dx.doi.org/10.1074/jbc.M110.110940] [PMID: 20466727]
[104]
Puangmalai, N.; Sengupta, U.; Bhatt, N.; Gaikwad, S.; Montalbano, M.; Bhuyan, A.; Garcia, S.; McAllen, S.; Sonawane, M.; Jerez, C.; Zhao, Y.; Kayed, R. Lysine 63-linked ubiquitination of tau oligomers contributes to the pathogenesis of Alzheimer’s disease. J. Biol. Chem., 2022, 298(4), 101766.
[http://dx.doi.org/10.1016/j.jbc.2022.101766] [PMID: 35202653]
[105]
Perry, G.; Friedman, R.; Shaw, G.; Chau, V. Ubiquitin is detected in neurofibrillary tangles and senile plaque neurites of Alzheimer disease brains. Proc. Natl. Acad. Sci. USA, 1987, 84(9), 3033-3036.
[http://dx.doi.org/10.1073/pnas.84.9.3033] [PMID: 3033674]
[106]
García-Sierra, F.; Jarero-Basulto, J.J.; Kristofikova, Z.; Majer, E.; Binder, L.I.; Ripova, D. Ubiquitin is associated with early truncation of tau protein at aspartic acid(421) during the maturation of neurofibrillary tangles in Alzheimer’s disease. Brain Pathol., 2012, 22(2), 240-250.
[http://dx.doi.org/10.1111/j.1750-3639.2011.00525.x] [PMID: 21919991]
[107]
Chakrabarty, R.; Yousuf, S.; Singh, M.P. Contributive role of hyperglycemia and hypoglycemia towards the development of alzheimer’s disease. Mol. Neurobiol., 2022, 59(7), 4274-4291.
[http://dx.doi.org/10.1007/s12035-022-02846-y] [PMID: 35503159]
[108]
Weeraratna, A.T.; Kalehua, A.; DeLeon, I.; Bertak, D.; Maher, G.; Wade, M.S.; Lustig, A.; Becker, K.G.; Wood, W., III; Walker, D.G.; Beach, T.G.; Taub, D.D. Alterations in immunological and neurological gene expression patterns in Alzheimer’s disease tissues. Exp. Cell Res., 2007, 313(3), 450-461.
[http://dx.doi.org/10.1016/j.yexcr.2006.10.028] [PMID: 17188679]
[109]
Chenfei, Z.; Haizhen, Y.; Jie, X.; Na, Z.; Bo, X. Effects of aerobic exercise on hippocampal SUMOylation in APP/PS1 transgenic mice. Neurosci. Lett., 2022, 767, 136303.
[http://dx.doi.org/10.1016/j.neulet.2021.136303] [PMID: 34695453]
[110]
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]
[111]
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]
[112]
Nagaraju, P.G.; Priyadarshini, P. Tau-aggregation inhibition: Promising role of nanoencapsulated dietary molecules in the management of Alzheimer’s disease. Crit. Rev. Food Sci. Nutr., 2023, 63(32), 11153-11168.
[PMID: 35748395]
[113]
Qin, M.; Li, H.; Bao, J.; Xia, Y.; Ke, D.; Wang, Q.; Liu, R.; Wang, J.Z.; Zhang, B.; Shu, X.; Wang, X. SET SUMOylation promotes its cytoplasmic retention and induces tau pathology and cognitive impairments. Acta Neuropathol. Commun., 2019, 7(1), 21.
[http://dx.doi.org/10.1186/s40478-019-0663-0] [PMID: 30767764]
[114]
Orsini, F. SUMO2 protects against tau-induced synaptic and cognitive dysfunction. bioRxiv, 2022.
[http://dx.doi.org/10.1101/2022.11.11.516192]
[115]
Kovacech, B.; Novak, M. Tau truncation is a productive posttranslational modification of neurofibrillary degeneration in Alzheimer’s disease. Curr. Alzheimer Res., 2010, 7(8), 708-716.
[http://dx.doi.org/10.2174/156720510793611556] [PMID: 20678071]
[116]
Abraha, A.; Ghoshal, N.; Gamblin, T.C.; Cryns, V.; Berry, R.W.; Kuret, J.; Binder, L.I. C-terminal inhibition of tau assembly in vitro and in Alzheimer’s disease. J. Cell Sci., 2000, 113(21), 3737-3745.
[http://dx.doi.org/10.1242/jcs.113.21.3737] [PMID: 11034902]
[117]
Novak, M.; Kabat, J.; Wischik, C.M. Molecular characterization of the minimal protease resistant tau unit of the Alzheimer’s disease paired helical filament. EMBO J., 1993, 12(1), 365-370.
[http://dx.doi.org/10.1002/j.1460-2075.1993.tb05665.x] [PMID: 7679073]
[118]
Loon, A.; Zamudio, F.; Sanneh, A.; Brown, B.; Smeltzer, S.; Brownlow, M.L.; Quadri, Z.; Peters, M.; Weeber, E.; Nash, K.; Lee, D.C.; Gordon, M.N.; Morgan, D.; Selenica, M.L.B. Accumulation of C-terminal cleaved tau is distinctly associated with cognitive deficits, synaptic plasticity impairment, and neurodegeneration in aged mice. Geroscience, 2022, 44(1), 173-194.
[http://dx.doi.org/10.1007/s11357-021-00408-z] [PMID: 34410588]
[119]
Wischik, C.M.; Novak, M.; Thøgersen, H.C.; Edwards, P.C.; Runswick, M.J.; Jakes, R.; Walker, J.E.; Milstein, C.; Roth, M.; Klug, A. Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease. Proc. Natl. Acad. Sci. USA, 1988, 85(12), 4506-4510.
[http://dx.doi.org/10.1073/pnas.85.12.4506] [PMID: 3132715]
[120]
Horta-Lopez, P.H. Association of α-1-antichymotrypsin expression with the development of conformational changes of tau protein in alzheimer's disease brain. Neuroscience, 2023, 518, 83-100.
[http://dx.doi.org/10.1016/j.neuroscience.2022.01.002]
[121]
Flores-Rodríguez, P.; Ontiveros-Torres, M.A.; Cárdenas-Aguayo, M.C.; Luna-Arias, J.P.; Meraz-Ríos, M.A.; Viramontes-Pintos, A.; Harrington, C.R.; Wischik, C.M.; Mena, R.; Florán-Garduño, B.; Luna-Muñoz, J. The relationship between truncation and phosphorylation at the C-terminus of tau protein in the paired helical filaments of Alzheimer’s disease. Front. Neurosci., 2015, 9, 33.
[http://dx.doi.org/10.3389/fnins.2015.00033] [PMID: 25717290]
[122]
Gu, J.; Xu, W.; Jin, N.; Li, L.; Zhou, Y.; Chu, D.; Gong, C.X.; Iqbal, K.; Liu, F. Truncation of Tau selectively facilitates its pathological activities. J. Biol. Chem., 2020, 295(40), 13812-13828.
[http://dx.doi.org/10.1074/jbc.RA120.012587] [PMID: 32737201]
[123]
Ngian, Z.K.; Tan, Y.Y.; Choo, C.T.; Lin, W.Q.; Leow, C.Y.; Mah, S.J.; Lai, M.K.P.; Chen, C.L.H.; Ong, C.T. Truncated Tau caused by intron retention is enriched in Alzheimer’s disease cortex and exhibits altered biochemical properties. Proc. Natl. Acad. Sci. USA, 2022, 119(37), e2204179119.
[http://dx.doi.org/10.1073/pnas.2204179119] [PMID: 36067305]
[124]
Lo, C.H. Heterogeneous tau oligomers as molecular targets for alzheimer’s disease and related tauopathies. Biophysica, 2022, 2(4), 440-451.
[http://dx.doi.org/10.3390/biophysica2040039]
[125]
Novak, P.; Cehlar, O.; Skrabana, R.; Novak, M. Tau conformation as a target for disease-modifying therapy: The role of truncation. J. Alzheimers Dis., 2018, 64(s1), S535-S546.
[http://dx.doi.org/10.3233/JAD-179942] [PMID: 29865059]
[126]
Smet-Nocca, C.; Broncel, M.; Wieruszeski, J.M.; Tokarski, C.; Hanoulle, X.; Leroy, A.; Landrieu, I.; Rolando, C.; Lippens, G.; Hackenberger, C.P.R. Identification of O-GlcNAc sites within peptides of the Tau protein and their impact on phosphorylation. Mol. Biosyst., 2011, 7(5), 1420-1429.
[http://dx.doi.org/10.1039/c0mb00337a] [PMID: 21327254]
[127]
Sato, Y.; Naito, Y.; Grundke-Iqbal, I.; Iqbal, K.; Endo, T. Analysis of N -glycans of pathological tau: Possible occurrence of aberrant processing of tau in Alzheimer’s disease. FEBS Lett., 2001, 496(2-3), 152-160.
[http://dx.doi.org/10.1016/S0014-5793(01)02421-8] [PMID: 11356201]
[128]
Ledesma, M.D.; Bonay, P.; Colaço, C.; Avila, J. Analysis of microtubule-associated protein tau glycation in paired helical filaments. J. Biol. Chem., 1994, 269(34), 21614-21619.
[http://dx.doi.org/10.1016/S0021-9258(17)31849-5] [PMID: 8063802]
[129]
Liu, K.; Liu, Y.; Li, L.; Qin, P.; Iqbal, J.; Deng, Y.; Qing, H. Glycation alter the process of Tau phosphorylation to change Tau isoforms aggregation property. Biochim. Biophys. Acta Mol. Basis Dis., 2016, 1862(2), 192-201.
[http://dx.doi.org/10.1016/j.bbadis.2015.12.002] [PMID: 26655600]
[130]
Ko, L.; Ko, E.C.; Nacharaju, P.; Liu, W.K.; Chang, E.; Kenessey, A.; Yen, S.H.C. An immunochemical study on tau glycation in paired helical filaments. Brain Res., 1999, 830(2), 301-313.
[http://dx.doi.org/10.1016/S0006-8993(99)01415-8] [PMID: 10366687]
[131]
Rungratanawanich, W.; Qu, Y.; Wang, X.; Essa, M.M.; Song, B.J. Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury. Exp. Mol. Med., 2021, 53(2), 168-188.
[http://dx.doi.org/10.1038/s12276-021-00561-7] [PMID: 33568752]
[132]
Lüth, H.J.; Ogunlade, V.; Kuhla, B.; Kientsch-Engel, R.; Stahl, P.; Webster, J.; Arendt, T.; Münch, G. Age- and stage-dependent accumulation of advanced glycation end products in intracellular deposits in normal and Alzheimer’s disease brains. Cereb. Cortex, 2004, 15(2), 211-220.
[http://dx.doi.org/10.1093/cercor/bhh123] [PMID: 15238435]
[133]
Necula, M.; Kuret, J. Pseudophosphorylation and glycation of tau protein enhance but do not trigger fibrillization in vitro. J. Biol. Chem., 2004, 279(48), 49694-49703.
[http://dx.doi.org/10.1074/jbc.M405527200] [PMID: 15364924]
[134]
Yekta, R.; Sadeghi, L.; Dehghan, G. The role of non-enzymatic glycation on Tau-DNA interactions: Kinetic and mechanistic approaches. Int. J. Biol. Macromol., 2022, 207, 161-168.
[http://dx.doi.org/10.1016/j.ijbiomac.2022.02.178] [PMID: 35257729]
[135]
Limorenko, G.; Lashuel, H.A. Revisiting the grammar of Tau aggregation and pathology formation: How new insights from brain pathology are shaping how we study and target Tauopathies. Chem. Soc. Rev., 2022, 51(2), 513-565.
[http://dx.doi.org/10.1039/D1CS00127B] [PMID: 34889934]
[136]
Reynolds, M.R.; Berry, R.W.; Binder, L.I. Site-specific nitration and oxidative dityrosine bridging of the τ protein by peroxynitrite: Implications for Alzheimer’s disease. Biochemistry, 2005, 44(5), 1690-1700.
[http://dx.doi.org/10.1021/bi047982v] [PMID: 15683253]
[137]
Maina, M.B. Dityrosine cross-links are present in Alzheimer’s disease-derived tau oligomers and paired helical filaments (PHF) which promotes the stability of the PHF-core tau (297-391) in vitro. bioRxiv, 2022.
[http://dx.doi.org/10.1101/2022.05.28.493839]
[138]
Butterfield, D.A.; Reed, T.T.; Perluigi, M.; De Marco, C.; Coccia, R.; Keller, J.N.; Markesbery, W.R.; Sultana, R. Elevated levels of 3-nitrotyrosine in brain from subjects with amnestic mild cognitive impairment: Implications for the role of nitration in the progression of Alzheimer’s disease. Brain Res., 2007, 1148, 243-248.
[http://dx.doi.org/10.1016/j.brainres.2007.02.084] [PMID: 17395167]
[139]
Reynolds, M.R.; Berry, R.W.; Binder, L.I. Site-specific nitration differentially influences τ assembly in vitro. Biochemistry, 2005, 44(42), 13997-14009.
[http://dx.doi.org/10.1021/bi051028w] [PMID: 16229489]
[140]
Zhang, Y.J.; Xu, Y.F.; Liu, Y.H.; Yin, J.; Li, H.L.; Wang, Q.; Wang, J.Z. Peroxynitrite induces Alzheimer-like tau modifications and accumulation in rat brain and its underlying mechanisms. FASEB J., 2006, 20(9), 1431-1442.
[http://dx.doi.org/10.1096/fj.05-5223com] [PMID: 16816118]
[141]
Weismiller, H.A.; Holub, T.J.; Krzesinski, B.J.; Margittai, M. A thiol-based intramolecular redox switch in four-repeat tau controls fibril assembly and disassembly. J. Biol. Chem., 2021, 297(3), 101021.
[http://dx.doi.org/10.1016/j.jbc.2021.101021] [PMID: 34339733]
[142]
Prifti, E. Mical modulates Tau toxicity via cysteine oxidation in vivo. Acta Neuropathol. Commun., 2022, 10(1), 1-19.
[PMID: 34980260]
[143]
Schiffter, H.A. 5.41 - Pharmaceutical Proteins – Structure, Stability, and Formulation, in Comprehensive Biotechnology, 2nd ed; Academic Press: Burlington, 2011, pp. 521-541.
[144]
Watanabe, A.; Takio, K.; Ihara, Y. Deamidation and isoaspartate formation in smeared tau in paired helical filaments. Unusual properties of the microtubule-binding domain of tau. J. Biol. Chem., 1999, 274(11), 7368-7378.
[http://dx.doi.org/10.1074/jbc.274.11.7368] [PMID: 10066801]
[145]
Ebashi, M.; Toru, S.; Nakamura, A.; Kamei, S.; Yokota, T.; Hirokawa, K.; Uchihara, T. Detection of AD-specific four repeat tau with deamidated asparagine residue 279-specific fraction purified from 4R tau polyclonal antibody. Acta Neuropathol., 2019, 138(1), 163-166.
[http://dx.doi.org/10.1007/s00401-019-02012-0] [PMID: 31006065]
[146]
Dan, A.; Takahashi, M.; Masuda-Suzukake, M.; Kametani, F.; Nonaka, T.; Kondo, H.; Akiyama, H.; Arai, T.; Mann, D.M.A.; Saito, Y.; Hatsuta, H.; Murayama, S.; Hasegawa, M. Extensive deamidation at asparagine residue 279 accounts for weak immunoreactivity of tau with RD4 antibody in Alzheimer’s disease brain. Acta Neuropathol. Commun., 2013, 1(1), 54.
[http://dx.doi.org/10.1186/2051-5960-1-54] [PMID: 24252707]
[147]
Reynolds, M.R.; Reyes, J.F.; Fu, Y.; Bigio, E.H.; Guillozet-Bongaarts, A.L.; Berry, R.W.; Binder, L.I. Tau nitration occurs at tyrosine 29 in the fibrillar lesions of Alzheimer’s disease and other tauopathies. J. Neurosci., 2006, 26(42), 10636-10645.
[http://dx.doi.org/10.1523/JNEUROSCI.2143-06.2006] [PMID: 17050703]
[148]
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]
[149]
Noble, W.; Hanger, D.P.; Miller, C.C.J.; Lovestone, S. The importance of tau phosphorylation for neurodegenerative diseases. Front. Neurol., 2013, 4, 83.
[http://dx.doi.org/10.3389/fneur.2013.00083] [PMID: 23847585]
[150]
Sibille, N.; Huvent, I.; Fauquant, C.; Verdegem, D.; Amniai, L.; Leroy, A.; Wieruszeski, J.M.; Lippens, G.; Landrieu, I. Structural characterization by nuclear magnetic resonance of the impact of phosphorylation in the proline-rich region of the disordered Tau protein. Proteins, 2012, 80(2), 454-462.
[http://dx.doi.org/10.1002/prot.23210] [PMID: 22072628]
[151]
Amniai, L.; Barbier, P.; Sillen, A.; Wieruszeski, J.M.; Peyrot, V.; Lippens, G.; Landrieu, I. Alzheimer disease specific phosphoepitopes of Tau interfere with assembly of tubulin but not binding to microtubules. FASEB J., 2009, 23(4), 1146-1152.
[http://dx.doi.org/10.1096/fj.08-121590] [PMID: 19074508]
[152]
Goode, B.L.; Denis, P.E.; Panda, D.; Radeke, M.J.; Miller, H.P.; Wilson, L.; Feinstein, S.C. Functional interactions between the proline-rich and repeat regions of tau enhance microtubule binding and assembly. Mol. Biol. Cell, 1997, 8(2), 353-365.
[http://dx.doi.org/10.1091/mbc.8.2.353] [PMID: 9190213]
[153]
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]
[154]
Rani, L.; Mallajosyula, S.S. Phosphorylation-induced structural reorganization in tau-paired helical filaments. ACS Chem. Neurosci., 2021, 12(9), 1621-1631.
[http://dx.doi.org/10.1021/acschemneuro.1c00084] [PMID: 33877805]
[155]
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]
[156]
Brotzakis, Z.F.; Lindstedt, P.R.; Taylor, R.J.; Rinauro, D.J.; Gallagher, N.C.T.; Bernardes, G.J.L.; Vendruscolo, M. A structural ensemble of a tau-microtubule complex reveals regulatory tau phosphorylation and acetylation mechanisms. ACS Cent. Sci., 2021, 7(12), 1986-1995.
[http://dx.doi.org/10.1021/acscentsci.1c00585] [PMID: 34963892]
[157]
Castro, T.G.; Ferreira, T.; Matamá, T.; Munteanu, F.D.; Cavaco-Paulo, A. Acetylation and phosphorylation processes modulate Tau’s binding to microtubules: A molecular dynamics study. Biochim. Biophys. Acta, Gen. Subj., 2023, 1867(2), 130276.
[http://dx.doi.org/10.1016/j.bbagen.2022.130276] [PMID: 36372288]
[158]
Leonard, C.; Phillips, C.; McCarty, J. Insight into seeded tau fibril growth from Molecular Dynamics simulation of the Alzheimer’s disease protofibril core. Front. Mol. Biosci., 2021, 8, 624302.
[http://dx.doi.org/10.3389/fmolb.2021.624302] [PMID: 33816551]
[159]
Munari, F.; Mollica, L.; Valente, C.; Parolini, F.; Kachoie, E.A.; Arrigoni, G.; D’Onofrio, M.; Capaldi, S.; Assfalg, M. Structural basis for chaperone-independent ubiquitination of tau protein by its E3 ligase CHIP. Angew. Chem. Int. Ed., 2022, 61(15), e202112374.
[http://dx.doi.org/10.1002/anie.202112374] [PMID: 35107860]
[160]
Mathew, A.T. N-glycosylation induced changes in tau protein dynamics reveal its role in tau misfolding and aggregation: A microsecond long molecular dynamics study. Proteins, 2022, 91(2), 147-162.
[http://dx.doi.org/10.26434/chemrxiv-2022-5bs5r]
[161]
Cummings, J.; Lee, G.; Ritter, A.; Sabbagh, M.; Zhong, K. Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement., 2019, 5(1), 272-293.
[http://dx.doi.org/10.1016/j.trci.2019.05.008] [PMID: 31334330]
[162]
Bush, A.I.; Tanzi, R.E. Therapeutics for Alzheimer’s disease based on the metal hypothesis. Neurotherapeutics, 2008, 5(3), 421-432.
[http://dx.doi.org/10.1016/j.nurt.2008.05.001] [PMID: 18625454]
[163]
Travis, J. Roche Alzheimer’s antibody fails to slow cognitive decline in major test; SCIENCEINSIDER, 2022.
[http://dx.doi.org/10.1126/science.adf8125]
[164]
Fellner, S.; Bauer, B.; Miller, D.S.; Schaffrik, M.; Fankhänel, M.; Spruß, T.; Bernhardt, G.; Graeff, C.; Färber, L.; Gschaidmeier, H.; Buschauer, A.; Fricker, G. Transport of paclitaxel (Taxol) across the blood-brain barrier in vitro and in vivo. J. Clin. Invest., 2002, 110(9), 1309-1318.
[http://dx.doi.org/10.1172/JCI0215451] [PMID: 12417570]
[165]
Sengupta, A.; Kabat, J.; Novak, M.; Wu, Q.; Grundke-Iqbal, I.; Iqbal, K. Phosphorylation of tau at both Thr 231 and Ser 262 is required for maximal inhibition of its binding to microtubules. Arch. Biochem. Biophys., 1998, 357(2), 299-309.
[http://dx.doi.org/10.1006/abbi.1998.0813] [PMID: 9735171]
[166]
Ishihara, T.; Hong, M.; Zhang, B.; Nakagawa, Y.; Lee, M.K.; Trojanowski, J.Q.; Lee, V.M.Y. Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform. Neuron, 1999, 24(3), 751-762.
[http://dx.doi.org/10.1016/S0896-6273(00)81127-7] [PMID: 10595524]
[167]
Schneider, A.; Biernat, J.; von Bergen, M.; Mandelkow, E.; Mandelkow, E.M. Phosphorylation that detaches tau protein from microtubules (Ser262, Ser214) also protects it against aggregation into Alzheimer paired helical filaments. Biochemistry, 1999, 38(12), 3549-3558.
[http://dx.doi.org/10.1021/bi981874p] [PMID: 10090741]
[168]
Ghoreschi, K.; Laurence, A.; O’Shea, J.J. Selectivity and therapeutic inhibition of kinases: To be or not to be? Nat. Immunol., 2009, 10(4), 356-360.
[http://dx.doi.org/10.1038/ni.1701] [PMID: 19295632]
[169]
Imahori, K.; Uchida, T. Physiology and pathology of tau protein kinases in relation to Alzheimer’s disease. J. Biochem., 1997, 121(2), 179-188.
[PMID: 9089387]
[170]
Hernández, F.; Borrell, J.; Guaza, C.; Avila, J.; Lucas, J.J. Spatial learning deficit in transgenic mice that conditionally over-express GSK-3β in the brain but do not form tau filaments. J. Neurochem., 2002, 83(6), 1529-1533.
[http://dx.doi.org/10.1046/j.1471-4159.2002.01269.x] [PMID: 12472906]
[171]
Lee, K.Y.; Clark, A.W.; Rosales, J.L.; Chapman, K.; Fung, T.; Johnston, R.N. Elevated neuronal Cdc2-like kinase activity in the Alzheimer disease brain. Neurosci. Res., 1999, 34(1), 21-29.
[http://dx.doi.org/10.1016/S0168-0102(99)00026-7] [PMID: 10413323]
[172]
Tseng, H.C.; Zhou, Y.; Shen, Y.; Tsai, L.H. A survey of Cdk5 activator p35 and p25 levels in Alzheimer’s disease brains. FEBS Lett., 2002, 523(1-3), 58-62.
[http://dx.doi.org/10.1016/S0014-5793(02)02934-4] [PMID: 12123804]
[173]
Noble, W.; Olm, V.; Takata, K.; Casey, E.; Mary, O.; Meyerson, J.; Gaynor, K.; LaFrancois, J.; Wang, L.; Kondo, T.; Davies, P.; Burns, M.; Veeranna; Nixon, R.; Dickson, D.; Matsuoka, Y.; Ahlijanian, M.; Lau, L.F.; Duff, K. Cdk5 is a key factor in tau aggregation and tangle formation in vivo. Neuron, 2003, 38(4), 555-565.
[http://dx.doi.org/10.1016/S0896-6273(03)00259-9] [PMID: 12765608]
[174]
Wen, Y.; Planel, E.; Herman, M.; Figueroa, H.Y.; Wang, L.; Liu, L.; Lau, L.F.; Yu, W.H.; Duff, K.E. Interplay between cyclin-dependent kinase 5 and glycogen synthase kinase 3 β mediated by neuregulin signaling leads to differential effects on tau phosphorylation and amyloid precursor protein processing. J. Neurosci., 2008, 28(10), 2624-2632.
[http://dx.doi.org/10.1523/JNEUROSCI.5245-07.2008] [PMID: 18322105]
[175]
Drewes, G.; Ebneth, A.; Preuss, U.; Mandelkow, E.M.; Mandelkow, E. MARK, a novel family of protein kinases that phosphorylate microtubule-associated proteins and trigger microtubule disruption. Cell, 1997, 89(2), 297-308.
[http://dx.doi.org/10.1016/S0092-8674(00)80208-1] [PMID: 9108484]
[176]
Noble, W.; Planel, E.; Zehr, C.; Olm, V.; Meyerson, J.; Suleman, F.; Gaynor, K.; Wang, L.; LaFrancois, J.; Feinstein, B.; Burns, M.; Krishnamurthy, P.; Wen, Y.; Bhat, R.; Lewis, J.; Dickson, D.; Duff, K. Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo. Proc. Natl. Acad. Sci. USA, 2005, 102(19), 6990-6995.
[http://dx.doi.org/10.1073/pnas.0500466102] [PMID: 15867159]
[177]
Hampel, H.; Ewers, M.; Bürger, K.; Annas, P.; Mörtberg, A.; Bogstedt, A.; Frölich, L.; Schröder, J.; Schönknecht, P.; Riepe, M.W.; Kraft, I.; Gasser, T.; Leyhe, T.; Möller, H.J.; Kurz, A.; Basun, H. Lithium trial in Alzheimer’s disease: A randomized, single-blind, placebo-controlled, multicenter 10-week study. J. Clin. Psychiatry, 2009, 70(6), 922-931.
[http://dx.doi.org/10.4088/JCP.08m04606] [PMID: 19573486]
[178]
Gitlin, M. Lithium side effects and toxicity: Prevalence and management strategies. Int. J. Bipolar Disord., 2016, 4(1), 27.
[http://dx.doi.org/10.1186/s40345-016-0068-y] [PMID: 27900734]
[179]
Bhat, R.; Xue, Y.; Berg, S.; Hellberg, S.; Ormö, M.; Nilsson, Y.; Radesäter, A.C.; Jerning, E.; Markgren, P.O.; Borgegård, T.; Nylöf, M.; Giménez-Cassina, A.; Hernández, F.; Lucas, J.J.; Díaz-Nido, J.; Avila, J. Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418. J. Biol. Chem., 2003, 278(46), 45937-45945.
[http://dx.doi.org/10.1074/jbc.M306268200] [PMID: 12928438]
[180]
Nakashima, H.; Ishihara, T.; Suguimoto, P.; Yokota, O.; Oshima, E.; Kugo, A.; Terada, S.; Hamamura, T.; Trojanowski, J.Q.; Lee, V.M.Y.; Kuroda, S. Chronic lithium treatment decreases tau lesions by promoting ubiquitination in a mouse model of tauopathies. Acta Neuropathol., 2005, 110(6), 547-556.
[http://dx.doi.org/10.1007/s00401-005-1087-4] [PMID: 16228182]
[181]
Engel, T.; Goñi-Oliver, P.; Lucas, J.J.; Avila, J.; Hernández, F. Chronic lithium administration to FTDP-17 tau and GSK-3β overexpressing mice prevents tau hyperphosphorylation and neurofibrillary tangle formation, but pre-formed neurofibrillary tangles do not revert. J. Neurochem., 2006, 99(6), 1445-1455.
[http://dx.doi.org/10.1111/j.1471-4159.2006.04139.x] [PMID: 17059563]
[182]
Selenica, M-L.; Jensen, H.S.; Larsen, A.K.; Pedersen, M.L.; Helboe, L.; Leist, M.; Lotharius, J. Efficacy of small-molecule glycogen synthase kinase-3 inhibitors in the postnatal rat model of tau hyperphosphorylation. Br. J. Pharmacol., 2007, 152(6), 959-979.
[http://dx.doi.org/10.1038/sj.bjp.0707471] [PMID: 17906685]
[183]
Naujok, O.; Lentes, J.; Diekmann, U.; Davenport, C.; Lenzen, S. Cytotoxicity and activation of the Wnt/beta-catenin pathway in mouse embryonic stem cells treated with four GSK3 inhibitors. BMC Res. Notes, 2014, 7(1), 273.
[http://dx.doi.org/10.1186/1756-0500-7-273] [PMID: 24779365]
[184]
Navarro-Retamal, C.; Caballero, J. Molecular modeling of tau proline-directed protein kinase (PDPK) inhibitors. In: Computational Modeling of Drugs Against Alzheimer’s Disease; Roy, K., Ed.; Springer New York: New York, NY, 2018; pp. 305-345.
[http://dx.doi.org/10.1007/978-1-4939-7404-7_13]
[185]
Congdon, E.E.; Sigurdsson, E.M. Tau-targeting therapies for Alzheimer disease. Nat. Rev. Neurol., 2018, 14(7), 399-415.
[http://dx.doi.org/10.1038/s41582-018-0013-z] [PMID: 29895964]
[186]
Courade, J.P.; Angers, R.; Mairet-Coello, G.; Pacico, N.; Tyson, K.; Lightwood, D.; Munro, R.; McMillan, D.; Griffin, R.; Baker, T.; Starkie, D.; Nan, R.; Westwood, M.; Mushikiwabo, M.L.; Jung, S.; Odede, G.; Sweeney, B.; Popplewell, A.; Burgess, G.; Downey, P.; Citron, M. Epitope determines efficacy of therapeutic anti-Tau antibodies in a functional assay with human Alzheimer Tau. Acta Neuropathol., 2018, 136(5), 729-745.
[http://dx.doi.org/10.1007/s00401-018-1911-2] [PMID: 30238240]
[187]
Jadhav, S.; Avila, J.; Schöll, M.; Kovacs, G.G.; Kövari, E.; Skrabana, R.; Evans, L.D.; Kontsekova, E.; Malawska, B.; de Silva, R.; Buee, L.; Zilka, N. A walk through tau therapeutic strategies. Acta Neuropathol. Commun., 2019, 7(1), 22.
[http://dx.doi.org/10.1186/s40478-019-0664-z] [PMID: 30767766]
[188]
Pradeepkiran, J.; Reddy, P. Structure based design and molecular docking studies for phosphorylated tau inhibitors in alzheimer’s disease. Cells, 2019, 8(3), 260.
[http://dx.doi.org/10.3390/cells8030260] [PMID: 30893872]
[189]
Halliday, M.; Radford, H.; Zents, K.A.M.; Molloy, C.; Moreno, J.A.; Verity, N.C.; Smith, E.; Ortori, C.A.; Barrett, D.A.; Bushell, M.; Mallucci, G.R. Repurposed drugs targeting eIF2α-P-mediated translational repression prevent neurodegeneration in mice. Brain, 2017, 140(6), 1768-1783.
[http://dx.doi.org/10.1093/brain/awx074] [PMID: 28430857]
[190]
SantaCruz, K.; Lewis, J.; Spires, T.; Paulson, J.; Kotilinek, L.; Ingelsson, M.; Guimaraes, A.; DeTure, M.; Ramsden, M.; McGowan, E.; Forster, C.; Yue, M.; Orne, J.; Janus, C.; Mariash, A.; Kuskowski, M.; Hyman, B.; Hutton, M.; Ashe, K.H. Tau suppression in a neurodegenerative mouse model improves memory function. Science, 2005, 309(5733), 476-481.
[http://dx.doi.org/10.1126/science.1113694] [PMID: 16020737]
[191]
Guo, N.; Peng, Z. MG132, a proteasome inhibitor, induces apoptosis in tumor cells. Asia Pac. J. Clin. Oncol., 2013, 9(1), 6-11.
[http://dx.doi.org/10.1111/j.1743-7563.2012.01535.x] [PMID: 22897979]
[192]
Choi, H.; Kim, H.J.; Yang, J.; Chae, S.; Lee, W.; Chung, S.; Kim, J.; Choi, H.; Song, H.; Lee, C.K.; Jun, J.H.; Lee, Y.J.; Lee, K.; Kim, S.; Sim, H.; Choi, Y.I.; Ryu, K.H.; Park, J.C.; Lee, D.; Han, S.H.; Hwang, D.; Kyung, J.; Mook-Jung, I. Acetylation changes tau interactome to degrade tau in Alzheimer’s disease animal and organoid models. Aging Cell, 2020, 19(1), e13081.
[http://dx.doi.org/10.1111/acel.13081] [PMID: 31763743]
[193]
Tarjányi, O.; Haerer, J.; Vecsernyés, M.; Berta, G.; Stayer-Harci, A.; Balogh, B.; Farkas, K.; Boldizsár, F.; Szeberényi, J.; Sétáló, G., Jr Prolonged treatment with the proteasome inhibitor MG-132 induces apoptosis in PC12 rat pheochromocytoma cells. Sci. Rep., 2022, 12(1), 5808.
[http://dx.doi.org/10.1038/s41598-022-09763-z] [PMID: 35388084]
[194]
Ohkusu-Tsukada, K.; Ito, D.; Takahashi, K. The role of proteasome inhibitor MG132 in 2,4-dinitrofluorobenzene-induced atopic dermatitis in NC/Nga mice. Int. Arch. Allergy Immunol., 2018, 176(2), 91-100.
[http://dx.doi.org/10.1159/000488155] [PMID: 29669333]
[195]
Corpas, R.; Griñán-Ferré, C.; Palomera-Ávalos, V.; Porquet, D.; de Frutos, P.G.; Cozzolino, S.M.F.; Rodríguez-Farré, E.; Pallàs, M.; Sanfeliu, C.; Cardoso, B.R. Melatonin induces mechanisms of brain resilience against neurodegeneration. J. Pineal Res., 2018, 65(4), e12515.
[http://dx.doi.org/10.1111/jpi.12515] [PMID: 29907977]
[196]
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]
[197]
Nixon, R.A. Autophagy in neurodegenerative disease: Friend, foe or turncoat? Trends Neurosci., 2006, 29(9), 528-535.
[http://dx.doi.org/10.1016/j.tins.2006.07.003] [PMID: 16859759]
[198]
Penke, B.; Bogár, F.; Crul, T.; Sántha, M.; Tóth, M.; Vígh, L. Heat shock proteins and autophagy pathways in neuroprotection: From molecular bases to pharmacological interventions. Int. J. Mol. Sci., 2018, 19(1), 325.
[http://dx.doi.org/10.3390/ijms19010325] [PMID: 29361800]
[199]
Dickey, C.A.; Dunmore, J.; Lu, B.; Wang, J.W.; Lee, W.C.; Kamal, A.; Burrows, F.; Eckman, C.; Hutton, M.; Petrucelli, L. HSP induction mediates selective clearance of tau phosphorylated at proline-directed Ser/Thr sites but not KXGS (MARK) sites. FASEB J., 2006, 20(6), 753-755.
[http://dx.doi.org/10.1096/fj.05-5343fje] [PMID: 16464956]
[200]
Zhang, H.; Burrows, F. Targeting multiple signal transduction pathways through inhibition of Hsp90. J. Mol. Med., 2004, 82(8), 488-499.
[http://dx.doi.org/10.1007/s00109-004-0549-9] [PMID: 15168026]
[201]
Jilani, K.; Qadri, S.M.; Lang, F. Geldanamycin-induced phosphatidylserine translocation in the erythrocyte membrane. Cell. Physiol. Biochem., 2013, 32(6), 1600-1609.
[http://dx.doi.org/10.1159/000356596] [PMID: 24335345]
[202]
Ochel, H.J.; Eichhorn, K.; Gademann, G. Geldanamycin: The prototype of a class of antitumor drugs targeting the heat shock protein 90 family of molecular chaperones. Cell Stress Chaperones, 2001, 6(2), 105-112.
[http://dx.doi.org/10.1379/1466-1268(2001)006<0105:GTPOAC>2.0.CO;2] [PMID: 11599571]
[203]
Kamal, A.; Thao, L.; Sensintaffar, J.; Zhang, L.; Boehm, M.F.; Fritz, L.C.; Burrows, F.J. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature, 2003, 425(6956), 407-410.
[http://dx.doi.org/10.1038/nature01913] [PMID: 14508491]
[204]
Vilenchik, M.; Solit, D.; Basso, A.; Huezo, H.; Lucas, B.; He, H.; Rosen, N.; Spampinato, C.; Modrich, P.; Chiosis, G. Targeting wide-range oncogenic transformation via PU24FCl, a specific inhibitor of tumor Hsp90. Chem. Biol., 2004, 11(6), 787-797.
[http://dx.doi.org/10.1016/j.chembiol.2004.04.008] [PMID: 15217612]
[205]
Hamano, T.; Gendron, T.F.; Causevic, E.; Yen, S.H.; Lin, W.L.; Isidoro, C.; DeTure, M.; Ko, L. Autophagic-lysosomal perturbation enhances tau aggregation in transfectants with induced wild- type tau expression. Eur. J. Neurosci., 2008, 27(5), 1119-1130.
[http://dx.doi.org/10.1111/j.1460-9568.2008.06084.x] [PMID: 18294209]
[206]
Berger, Z.; Ravikumar, B.; Menzies, F.M.; Oroz, L.G.; Underwood, B.R.; Pangalos, M.N.; Schmitt, I.; Wullner, U.; Evert, B.O.; O’Kane, C.J.; Rubinsztein, D.C. Rapamycin alleviates toxicity of different aggregate-prone proteins. Hum. Mol. Genet., 2006, 15(3), 433-442.
[http://dx.doi.org/10.1093/hmg/ddi458] [PMID: 16368705]
[207]
Morita, T.; Sobue, K. Specification of neuronal polarity regulated by local translation of CRMP2 and Tau via the mTOR-p70S6K pathway. J. Biol. Chem., 2009, 284(40), 27734-27745.
[http://dx.doi.org/10.1074/jbc.M109.008177] [PMID: 19648118]
[208]
Bresinsky, M.; Strasser, J.M.; Vallaster, B.; Liu, P.; McCue, W.M.; Fuller, J.; Hubmann, A.; Singh, G.; Nelson, K.M.; Cuellar, M.E.; Wilmot, C.M.; Finzel, B.C.; Ashe, K.H.; Walters, M.A.; Pockes, S. Structure-based design and biological evaluation of novel caspase-2 inhibitors based on the peptide AcVDVAD-CHO and the caspase-2-mediated tau cleavage sequence YKPVD314. ACS Pharmacol. Transl. Sci., 2022, 5(1), 20-40.
[http://dx.doi.org/10.1021/acsptsci.1c00251] [PMID: 35059567]
[209]
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]
[210]
Yu, Y.; Zhang, L.; Li, X.; Run, X.; Liang, Z.; Li, Y.; Liu, Y.; Lee, M.H.; Grundke-Iqbal, I.; Iqbal, K.; Vocadlo, D.J.; Liu, F.; Gong, C.X. Differential effects of an O-GlcNAcase inhibitor on tau phosphorylation. PLoS One, 2012, 7(4), e35277.
[http://dx.doi.org/10.1371/journal.pone.0035277] [PMID: 22536363]
[211]
Selnick, H.G.; Hess, J.F.; Tang, C.; Liu, K.; Schachter, J.B.; Ballard, J.E.; Marcus, J.; Klein, D.J.; Wang, X.; Pearson, M.; Savage, M.J.; Kaul, R.; Li, T.S.; Vocadlo, D.J.; Zhou, Y.; Zhu, Y.; Mu, C.; Wang, Y.; Wei, Z.; Bai, C.; Duffy, J.L.; McEachern, E.J. Discovery of MK-8719, a potent o-glcnacase inhibitor as a potential treatment for tauopathies. J. Med. Chem., 2019, 62(22), 10062-10097.
[http://dx.doi.org/10.1021/acs.jmedchem.9b01090] [PMID: 31487175]
[212]
ASN90 2022. Available from: https://www.alzforum.org/therapeutics/asn90
[213]
Yuzwa, S.A.; Shan, X.; Macauley, M.S.; Clark, T.; Skorobogatko, Y.; Vosseller, K.; Vocadlo, D.J. Increasing O-GlcNAc slows neurodegeneration and stabilizes tau against aggregation. Nat. Chem. Biol., 2012, 8(4), 393-399.
[http://dx.doi.org/10.1038/nchembio.797] [PMID: 22366723]
[214]
Younes, M.; Aggett, P.; Aguilar, F.; Crebelli, R.; Dusemund, B.; Filipič, M.; Frutos, M.J.; Galtier, P.; Gott, D.; Gundert-Remy, U.; Lambré, C.; Leblanc, J.C.; Lillegaard, I.T.; Moldeus, P.; Mortensen, A.; Oskarsson, A.; Stankovic, I.; Waalkens-Berendsen, I.; Woutersen, R.A.; Andrade, R.J.; Fortes, C.; Mosesso, P.; Restani, P.; Arcella, D.; Pizzo, F.; Smeraldi, C.; Wright, M. Scientific opinion on the safety of green tea catechins. EFSA J., 2018, 16(4), e05239.
[PMID: 32625874]
[215]
Mereles, D.; Hunstein, W. Epigallocatechin-3-gallate (EGCG) for clinical trials: More pitfalls than promises? Int. J. Mol. Sci., 2011, 12(9), 5592-5603.
[http://dx.doi.org/10.3390/ijms12095592] [PMID: 22016611]
[216]
Sonawane, S.K.; Chinnathambi, S. Epigallocatechin-3-gallate modulates tau post-translational modifications and cytoskeletal network. Oncotarget, 2021, 12(11), 1083-1099.
[http://dx.doi.org/10.18632/oncotarget.27963] [PMID: 34084282]
[217]
Seidler, P.M.; Murray, K.A.; Boyer, D.R.; Ge, P.; Sawaya, M.R.; Hu, C.J.; Cheng, X.; Abskharon, R.; Pan, H.; DeTure, M.A.; Williams, C.K.; Dickson, D.W.; Vinters, H.V.; Eisenberg, D.S. Structure-based discovery of small molecules that disaggregate Alzheimer’s disease tissue derived tau fibrils in vitro. Nat. Commun., 2022, 13(1), 5451.
[http://dx.doi.org/10.1038/s41467-022-32951-4] [PMID: 36114178]
[218]
Inuzuka, H.; Liu, J.; Wei, W.; Rezaeian, A.H. PROTAC technology for the treatment of Alzheimer’s disease: Advances and perspectives. Acta Materia Medica, 2022, 1(1), 24-41.
[http://dx.doi.org/10.15212/AMM-2021-0001] [PMID: 35237768]
[219]
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]

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