Please wait a minute...
Shopping Cart Email List Chinese
Advanced Search Fig/Tab
Quantitative Biology

ISSN 2095-4689

ISSN 2095-4697(Online)

CN 10-1028/TM

Postal Subscription Code 80-971

Featured Articles  |  Most Downloaded  |  Most Reading
Online Submission Subscribe to Our RSS Content Feed
Quant. Biol.    2022, Vol. 10 Issue (1) : 17-34    https://doi.org/10.15302/J-QB-021-0271
REVIEW
Recent studies of atomic-resolution structures of tau protein and structure-based inhibitors
Lili Zhu, Zhenyu Qian()
Key Laboratory of Exercise and Health Sciences (Ministry of Education) and School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China
 Download: PDF(10788 KB)   HTML
 Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract

Background: Alzheimer’s disease (AD) is one of the most popular tauopathies. Neurofibrillary tangles and senile plaques are widely recognized as the pathological hallmarks of AD, which are mainly composed of tau and β-amyloid (Aβ) respectively. Recent failures of drugs targeting Aβ have led scientists to scrutinize the crucial impact of tau in neurodegenerative diseases. Mutated or abnormal phosphorylated tau protein loses affinity with microtubules and assembles into pathological accumulations. The aggregation process closely correlates to two amyloidogenic core of PHF6 (306VQIVYK311) and PHF6* (275VQIINK280) fragments. Moreover, tau accumulations display diverse morphological characteristics in different diseases, which increases the difficulty of providing a unifying neuropathological criterion for early diagnosis.

Results: This review mainly summarizes atomic-resolution structures of tau protein in the monomeric, oligomeric and fibrillar states, as well as the promising inhibitors designed to prevent tau aggregation or disaggregate tau accumulations, recently revealed by experimental and computational studies. We also systematically sort tau functions, their relationship with tau structures and the potential pathological processes of tau protein.

Conclusion: The current progress on tau structures at atomic level of detail expands our understanding of tau aggregation and related pathology. We discuss the difficulties in determining the source of neurotoxicity and screening effective inhibitors. We hope this review will inspire new clues for designing medicines against tau aggregation and shed light on AD diagnosis and therapies.
Keywords tau      paired helical filaments      inhibitor      cryo-electron microscopy      molecular dynamics simulation     
Corresponding Author(s): Zhenyu Qian   
About author:

Mingsheng Sun and Mingxiao Yang contributed equally to this work.
Just Accepted Date: 30 November 2021   Online First Date: 14 January 2022    Issue Date: 28 March 2022
 Cite this article:   
Lili Zhu,Zhenyu Qian. Recent studies of atomic-resolution structures of tau protein and structure-based inhibitors[J]. Quant. Biol., 2022, 10(1): 17-34.
 URL:  
https://academic.hep.com.cn/qb/EN/10.15302/J-QB-021-0271
https://academic.hep.com.cn/qb/EN/Y2022/V10/I1/17
Fig.1  The domains and isoforms of tau.
Fig.2  The process of tau aggregation.
Fig.3  Tau filaments in diseases.
Tab.1  The structure of small molecular inhibitors
Tab.2  The structure of nanoparticles and the sequence of short peptides employed as inhibitors
1 Q., Chen Y., Du K., Zhang Z., Liang J., Li H., Yu R., Ren J., Feng Z., Jin F. Li et al.. (2018). A tau-targeted multifunctional nanocomposite for combinational therapy of Alzheimer’s disease. ACS Nano, 12 : 1321–1338
https://doi.org/10.1021/acsnano.7b07625
2 J., Zeisel K. Bennett (2020). World Alzheimer report 2020: Design, dignity, dementia: dementia-related design and the built environment. Accessed: February 1, 2021
3 Association Alzheimer’s (2021). 2021 Alzheimer’s disease facts and figures. Alzheimers Dement., 17 : 327–406
https://doi.org/10.1002/alz.12328
4 J. Grandy (2013). Melatonin: Therapeutic intervention in mild cognitive impairment and Alzheimer disease. J. Neurol. Neurophysiol., 4 : 148
https://doi.org/10.4172/2155-9562.1000148
5 M. S., Uddin M. T., Kabir A., Al Mamun M. M., Abdel-Daim G. E. Barreto G. Ashraf (2019). APOE and Alzheimer’s disease: Evidence mounts that targeting APOE4 may combat Alzheimer’s pathogenesis. Mol. Neurobiol., 56 : 2450–2465
https://doi.org/10.1007/s12035-018-1237-z
6 J. A. Hardy G. Higgins (1992). Alzheimer’s disease: the amyloid cascade hypothesis. Science, 256 : 184–185
https://doi.org/10.1126/science.1566067
7 K., Rajasekhar M. Chakrabarti (2015). Function and toxicity of amyloid beta and recent therapeutic interventions targeting amyloid beta in Alzheimer’s disease. Chem. Commun. (Camb.), 51 : 13434–13450
https://doi.org/10.1039/C5CC05264E
8 K. Rajasekhar (2018). Current progress, challenges and future prospects of diagnostic and therapeutic interventions in Alzheimer’s disease. RSC Advances, 8 : 23780–23804
https://doi.org/10.1039/C8RA03620A
9 R., van der Kant L. S. B. Goldstein (2020). Amyloid-β-independent regulators of tau pathology in Alzheimer disease. Nat. Rev. Neurosci., 21 : 21–35
https://doi.org/10.1038/s41583-019-0240-3
10 E. E. Congdon E. Sigurdsson (2018). Tau-targeting therapies for Alzheimer disease. Nat. Rev. Neurol., 14 : 399–415
https://doi.org/10.1038/s41582-018-0013-z
11 S. M. Alavi Naini (2015). Tau hyperphosphorylation and oxidative stress, a critical vicious circle in neurodegenerative tauopathies? Oxid. Med. Cell. Longev., 2015 : 151979
https://doi.org/10.1155/2015/151979
12 J. S., Kerr B. A., Adriaanse N. H., Greig M. P., Mattson M. Z., Cader V. A. Bohr E. Fang (2017). Mitophagy and Alzheimer’s disease: Cellular and molecular mechanisms. Trends Neurosci., 40 : 151–166
https://doi.org/10.1016/j.tins.2017.01.002
13 M. A. Busche B. Hyman (2020). Synergy between amyloid-β and tau in Alzheimer’s disease. Nat. Neurosci., 23 : 1183–1193
https://doi.org/10.1038/s41593-020-0687-6
14 A. Mullard (2021). Failure of first anti-tau antibody in Alzheimer disease highlights risks of history repeating. Nat. Rev. Drug Discov., 20 : 3–5
https://doi.org/10.1038/d41573-020-00217-7
15 L. Dehmelt (2005). The MAP2/Tau family of microtubule-associated proteins. Genome Biol., 6 : 204
https://doi.org/10.1186/gb-2004-6-1-204
16 L., Jameson T., Frey B., Zeeberg F. Dalldorf (1980). Inhibition of microtubule assembly by phosphorylation of microtubule-associated proteins. Biochemistry, 19 : 2472–2479
https://doi.org/10.1021/bi00552a027
17 Y., Gu F. Oyama (1996). Tau is widely expressed in rat tissues. J. Neurochem., 67 : 1235–1244
https://doi.org/10.1046/j.1471-4159.1996.67031235.x
18 L. Bakota (2016). Tau biology and tau-directed therapies for Alzheimer’s disease. Drugs, 76 : 301–313
https://doi.org/10.1007/s40265-015-0529-0
19 T., Guo W. Noble D. Hanger (2017). Roles of tau protein in health and disease. Acta Neuropathol., 133 : 665–704
https://doi.org/10.1007/s00401-017-1707-9
20 M., Goedert M. G., Spillantini R., Jakes D. Rutherford R. Crowther (1989). Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer’s disease. Neuron, 3 : 519–526
https://doi.org/10.1016/0896-6273(89)90210-9
21 E. Mandelkow (2012). Biochemistry and cell biology of tau protein in neurofibrillary degeneration. Cold Spring Harb. Perspect. Med., 2 : a006247
https://doi.org/10.1101/cshperspect.a006247
22 C. Conde (2009). Microtubule assembly, organization and dynamics in axons and dendrites. Nat. Rev. Neurosci., 10 : 319–332
https://doi.org/10.1038/nrn2631
23 M. D., Weingarten A. H., Lockwood S. Y. Hwo M. Kirschner (1975). A protein factor essential for microtubule assembly. Proc. Natl. Acad. Sci. USA, 72 : 1858–1862
https://doi.org/10.1073/pnas.72.5.1858
24 T. G., Castro F. D. Munteanu (2019). Electrostatics of tau protein by molecular dynamics. Biomolecules, 9 : 116
https://doi.org/10.3390/biom9030116
25 E. H., Kellogg N. M. A., Hejab S., Poepsel K. H., Downing F. DiMaio (2018). Near-atomic model of microtubule-tau interactions. Science, 360 : 1242–1246
https://doi.org/10.1126/science.aat1780
26 Qiang, L., Sun, X., Austin, T. O., Muralidharan, H., Jean, D. C., Liu, M., Yu, W., and Baas, P. W. (2018) Tau does not stabilize axonal microtubules but rather enables them to have long labile domains. Curr. Biol., 28, 2181−2189. e4
27 P. W. Baas (2019). Tau: It’s not what you think. Trends Cell Biol., 29 : 452–461
https://doi.org/10.1016/j.tcb.2019.02.007
28 G. B., Witman D. W., Cleveland M. D. Weingarten M. Kirschner (1976). Tubulin requires tau for growth onto microtubule initiating sites. Proc. Natl. Acad. Sci. USA, 73 : 4070–4074
https://doi.org/10.1073/pnas.73.11.4070
29 B., Zhang J., Carroll J. Q., Trojanowski Y., Yao M., Iba J. S., Potuzak A. M., Hogan S. X., Xie C., Ballatore A. B. Smith III et al.. (2012). The microtubule-stabilizing agent, epothilone D, reduces axonal dysfunction, neurotoxicity, cognitive deficits, and Alzheimer-like pathology in an interventional study with aged tau transgenic mice. J. Neurosci., 32 : 3601–3611
https://doi.org/10.1523/JNEUROSCI.4922-11.2012
30 A., Mietelska-Porowska U., Wasik M., Goras A. Filipek (2014). Tau protein modifications and interactions: their role in function and dysfunction. Int. J. Mol. Sci., 15 : 4671–4713
https://doi.org/10.3390/ijms15034671
31 M. Medina (2014). The role of extracellular tau in the spreading of neurofibrillary pathology. Front. Cell. Neurosci., 8 : 113
https://doi.org/10.3389/fncel.2014.00113
32 A., Elie E., Prezel C., rin E., Denarier S., Ramirez-Rios L., Serre A., Andrieux A., Fourest-Lieuvin L. Blanchoin (2015). Tau co-organizes dynamic microtubule and actin networks. Sci. Rep., 5 : 9964
https://doi.org/10.1038/srep09964
33 M., Violet L., Delattre M., Tardivel A., Sultan A., Chauderlier R., Caillierez S., Talahari F., Nesslany B., Lefebvre E. Bonnefoy et al.. (2014). A major role for tau in neuronal DNA and RNA protection in vivo under physiological and hyperthermic conditions. Front. Cell. Neurosci., 8 : 84
https://doi.org/10.3389/fncel.2014.00084
34 A., Sultan F., Nesslany M., Violet S., gard A., Loyens S., Talahari Z., Mansuroglu D., Marzin N., Sergeant S. Humez et al.. (2011). Nuclear tau, a key player in neuronal DNA protection. J. Biol. Chem., 286 : 4566–4575
https://doi.org/10.1074/jbc.M110.199976
35 B., Bulic M., Pickhardt E. M. Mandelkow (2010). Tau protein and tau aggregation inhibitors. Neuropharmacology, 59 : 276–289
https://doi.org/10.1016/j.neuropharm.2010.01.016
36 P. M., Seidler D. R., Boyer J. A., Rodriguez M. R., Sawaya D., Cascio K., Murray T. Gonen D. Eisenberg (2018). Structure-based inhibitors of tau aggregation. Nat. Chem., 10 : 170–176
https://doi.org/10.1038/nchem.2889
37 B., Nizynski W. Dzwolak (2017). Amyloidogenesis of tau protein. Protein Sci., 26 : 2126–2150
https://doi.org/10.1002/pro.3275
38 Y., Liu M., Nguyen A. Robert (2019). Metal ions in Alzheimer’s disease: A key role or not? Acc. Chem. Res., 52 : 2026–2035
https://doi.org/10.1021/acs.accounts.9b00248
39 A. M., Fanni C. M., Vander Zanden P. V., Majewska J. Majewski E. Chi (2019). Membrane-mediated fibrillation and toxicity of the tau hexapeptide PHF6. J. Biol. Chem., 294 : 15304–15317
https://doi.org/10.1074/jbc.RA119.010003
40 H. L., Zhu C., ndez J. B., Fan F., Shewmaker J., Chen A. P. Minton (2010). Quantitative characterization of heparin binding to tau protein: implication for inducer-mediated tau filament formation. J. Biol. Chem., 285 : 3592–3599
https://doi.org/10.1074/jbc.M109.035691
41 N., Kfoury B. B., Holmes H., Jiang D. M. Holtzman M. Diamond (2012). Trans-cellular propagation of tau aggregation by fibrillar species. J. Biol. Chem., 287 : 19440–19451
https://doi.org/10.1074/jbc.M112.346072
42 R., La Joie A. V., Visani S. L., Baker J. A., Brown V., Bourakova J., Cha K., Chaudhary L., Edwards L., Iaccarino M. Janabi et al.. (2020). Prospective longitudinal atrophy in Alzheimer’s disease correlates with the intensity and topography of baseline tau-PET. Sci. Transl. Med., 12 : eaau5732
https://doi.org/10.1126/scitranslmed.aau5732
43 C. C., Lee A., Nayak A., Sethuraman G. Belfort G. McRae (2007). A three-stage kinetic model of amyloid fibrillation. Biophys. J., 92 : 3448–3458
https://doi.org/10.1529/biophysj.106.098608
44 C., Iannuzzi M., Borriello G., Irace M., Cammarota A. Di Maro (2017). Vanillin affects amyloid aggregation and non-enzymatic glycation in human insulin. Sci. Rep., 7 : 15086
https://doi.org/10.1038/s41598-017-15503-5
45 H., Mirbaha D., Chen O. A., Morazova K. M., Ruff A. M., Sharma X., Liu M., Goodarzi R. V., Pappu D. W., Colby H. Mirzaei et al.. (2018). Inert and seed-competent tau monomers suggest structural origins of aggregation. eLife, 7 : e36584
https://doi.org/10.7554/eLife.36584
46 S. L., Shammas G. A., Garcia S., Kumar M., Kjaergaard M. H., Horrocks N., Shivji E., Mandelkow T. P., Knowles E. Mandelkow (2015). A mechanistic model of tau amyloid aggregation based on direct observation of oligomers. Nat. Commun., 6 : 7025
https://doi.org/10.1038/ncomms8025
47 M., Kjaergaard A. J., Dear F., Kundel S., Qamar G., Meisl T. P. J. Knowles (2018). Oligomer diversity during the aggregation of the repeat region of tau. ACS Chem. Neurosci., 9 : 3060–3071
https://doi.org/10.1021/acschemneuro.8b00250
48 A. Y., Roman F., Devred D., Byrne R., La Rocca N. N., Ninkina V. Peyrot P. Tsvetkov (2019). Zinc induces temperature-dependent reversible self-assembly of tau. J. Mol. Biol., 431 : 687–695
https://doi.org/10.1016/j.jmb.2018.12.008
49 S. K., Sonawane H., Chidambaram D., Boral N. V., Gorantla A. A., Balmik A., Dangi S., Ramasamy U. K. Marelli (2020). EGCG impedes human tau aggregation and interacts with Tau. Sci. Rep., 10 : 12579
https://doi.org/10.1038/s41598-020-69429-6
50 G. Ramachandran J. Udgaonkar (2011). Understanding the kinetic roles of the inducer heparin and of rod-like protofibrils during amyloid fibril formation by tau protein. J. Biol. Chem., 286 : 38948–38959
https://doi.org/10.1074/jbc.M111.271874
51 C. N., Chirita E. E., Congdon H. Yin (2005). Triggers of full-length tau aggregation: a role for partially folded intermediates. Biochemistry, 44 : 5862–5872
https://doi.org/10.1021/bi0500123
52 Y., Luo P., Dinkel X., Yu M., Margittai J., Zheng R., Nussinov G. Wei (2013). Molecular insights into the reversible formation of tau protein fibrils. Chem. Commun. (Camb.), 49 : 3582–3584
https://doi.org/10.1039/c3cc00241a
53 M., Goedert D. S. Eisenberg R. Crowther (2017). Propagation of tau aggregates and neurodegeneration. Annu. Rev. Neurosci., 40 : 189–210
https://doi.org/10.1146/annurev-neuro-072116-031153
54 A. W. P., Fitzpatrick B., Falcon S., He A. G., Murzin G., Murshudov H. J., Garringer R. A., Crowther B., Ghetti M. Goedert S. H. Scheres (2017). Cryo-EM structures of tau filaments from Alzheimer’s disease. Nature, 547 : 185–190
https://doi.org/10.1038/nature23002
55 B., Falcon W., Zhang M., Schweighauser A. G., Murzin R., Vidal H. J., Garringer B., Ghetti S. H. W. Scheres (2018). Tau filaments from multiple cases of sporadic and inherited Alzheimer’s disease adopt a common fold. Acta Neuropathol., 136 : 699–708
https://doi.org/10.1007/s00401-018-1914-z
56 M., Goedert B., Falcon W., Zhang B. Ghetti S. H. Scheres (2018). Distinct conformers of assembled tau in Alzheimer’s and Pick’s diseases. Cold Spring Harb. Symp. Quant. Biol., 83 : 163–171
https://doi.org/10.1101/sqb.2018.83.037580
57 B., Falcon W., Zhang A. G., Murzin G., Murshudov H. J., Garringer R., Vidal R. A., Crowther B., Ghetti S. H. W. Scheres (2018). Structures of filaments from Pick’s disease reveal a novel tau protein fold. Nature, 561 : 137–140
https://doi.org/10.1038/s41586-018-0454-y
58 B., Qi S., Jin H. Qian (2020). Bibliometric analysis of chronic traumatic encephalopathy research from 1999 to 2019. Int. J. Environ. Res. Public Health, 17 : 5411
https://doi.org/10.3390/ijerph17155411
59 B., Falcon J., Zivanov W., Zhang A. G., Murzin H. J., Garringer R., Vidal R. A., Crowther K. L., Newell B., Ghetti M. Goedert et al.. (2019). Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules. Nature, 568 : 420–423
https://doi.org/10.1038/s41586-019-1026-5
60 N., Sergeant A. Wattez (1999). Neurofibrillary degeneration in progressive supranuclear palsy and corticobasal degeneration: tau pathologies with exclusively “exon 10” isoforms. J. Neurochem., 72 : 1243–1249
https://doi.org/10.1046/j.1471-4159.1999.0721243.x
61 W., Zhang A., Tarutani K. L., Newell A. G., Murzin T., Matsubara B., Falcon R., Vidal H. J., Garringer Y., Shi T. Ikeuchi et al.. (2020). Novel tau filament fold in corticobasal degeneration. Nature, 580 : 283–287
https://doi.org/10.1038/s41586-020-2043-0
62 M. D., Mukrasch M., von Bergen J., Biernat D., Fischer C., Griesinger E. Mandelkow (2007). The “jaws” of the tau-microtubule interaction. J. Biol. Chem., 282 : 12230–12239
https://doi.org/10.1074/jbc.M607159200
63 M. D., Mukrasch S., Bibow J., Korukottu S., Jeganathan J., Biernat C., Griesinger E. Mandelkow (2009). Structural polymorphism of 441-residue tau at single residue resolution. PLoS Biol., 7 : e34
https://doi.org/10.1371/journal.pbio.1000034
64 D., Chen K. W., Drombosky Z., Hou L., Sari O. M., Kashmer B. D., Ryder V. A., Perez D. R., Woodard M. M., Lin M. I. Diamond et al.. (2019). Tau local structure shields an amyloid-forming motif and controls aggregation propensity. Nat. Commun., 10 : 2493
https://doi.org/10.1038/s41467-019-10355-1
65 R., Nelson M. R., Sawaya M., Balbirnie A. O., Madsen C., Riekel R. Grothe (2005). Structure of the cross-beta spine of amyloid-like fibrils. Nature, 435 : 773–778
https://doi.org/10.1038/nature03680
66 M. R., Sawaya S., Sambashivan R., Nelson M. I., Ivanova S. A., Sievers M. I., Apostol M. J., Thompson M., Balbirnie J. J., Wiltzius H. T. McFarlane et al.. (2007). Atomic structures of amyloid cross-beta spines reveal varied steric zippers. Nature, 447 : 453–457
https://doi.org/10.1038/nature05695
67 V. G., KrishnaKumar A., Paul E. Gazit (2018). Mechanistic insights into remodeled tau-derived PHF6 peptide fibrils by Naphthoquinone-Tryptophan hybrids. Sci. Rep., 8 : 71
https://doi.org/10.1038/s41598-017-18443-2
68 S. A., Sievers J., Karanicolas H. W., Chang A., Zhao L., Jiang O., Zirafi J. T., Stevens J., nch D. Baker (2011). Structure-based design of non-natural amino-acid inhibitors of amyloid fibril formation. Nature, 475 : 96–100
https://doi.org/10.1038/nature10154
69 M., Chemerovski-Glikman M., Frenkel-Pinter R., Mdah A., Abu-Mokh E. Gazit (2017). Inhibition of the aggregation and toxicity of the minimal amyloidogenic fragment of tau by its pro-substituted analogues. Chemistry, 23 : 9618–9624
https://doi.org/10.1002/chem.201701218
70 M., Pickhardt T., Neumann D., Schwizer K., Callaway M., Vendruscolo D., Schenk P., St George-Hyslop E. M., Mandelkow C. M., Dobson L. McConlogue et al.. (2015). Identification of small molecule inhibitors of tau aggregation by targeting monomeric tau as a potential therapeutic approach for tauopathies. Curr. Alzheimer Res., 12 : 814–828
https://doi.org/10.2174/156720501209151019104951
71 E. J., Davidowitz P. K., Krishnamurthy P., Lopez H., Jimenez L., Adrien P. Davies J. Moe (2020). In vivo validation of a small molecule inhibitor of tau self-association in htau mice. J. Alzheimers Dis., 73 : 147–161
https://doi.org/10.3233/JAD-190465
72 F., Kundel S., De P., Flagmeier M. H., Horrocks M., Kjaergaard S. L., Shammas S. E., Jackson C. M. Dobson (2018). Hsp70 inhibits the nucleation and elongation of tau and sequesters tau aggregates with high affinity. ACS Chem. Biol., 13 : 636–646
https://doi.org/10.1021/acschembio.7b01039
73 P. M., Seidler D. R., Boyer K. A., Murray T. P., Yang M., Bentzel M. R., Sawaya G., Rosenberg D., Cascio C. K., Williams K. L. Newell et al.. (2019). Structure-based inhibitors halt prion-like seeding by Alzheimer’s disease-and tauopathy-derived brain tissue samples. J. Biol. Chem., 294 : 16451–16464
https://doi.org/10.1074/jbc.RA119.009688
74 G., Larbig M., Pickhardt D. G., Lloyd B. Schmidt (2007). Screening for inhibitors of tau protein aggregation into Alzheimer paired helical filaments: a ligand based approach results in successful scaffold hopping. Curr. Alzheimer Res., 4 : 315–323
https://doi.org/10.2174/156720507781077250
75 G. K., Viswanathan D., Shwartz Y., Losev E., Arad C., Shemesh E., Pichinuk H., Engel A., Raveh R., Jelinek I. Cooper et al.. (2020). Purpurin modulates tau-derived VQIVYK fibrillization and ameliorates Alzheimer’s disease-like symptoms in animal model. Cell. Mol. Life Sci., 77 : 2795–2813
https://doi.org/10.1007/s00018-019-03312-0
76 Y., Porat A. Abramowitz (2006). Inhibition of amyloid fibril formation by polyphenols: structural similarity and aromatic interactions as a common inhibition mechanism. Chem. Biol. Drug Des., 67 : 27–37
https://doi.org/10.1111/j.1747-0285.2005.00318.x
77 N., Bijari S., Balalaie V., Akbari F., Golmohammadi S., Moradi H. Adibi (2018). Effective suppression of the modified PHF6 peptide/1N4R Tau amyloid aggregation by intact curcumin, not its degradation products: Another evidence for the pigment as preventive/therapeutic “functional food”. Int. J. Biol. Macromol., 120 : 1009–1022
https://doi.org/10.1016/j.ijbiomac.2018.08.175
78 J. S., Rane P. Bhaumik (2017). Curcumin inhibits tau aggregation and disintegrates preformed tau filaments in vitro. J. Alzheimers Dis., 60 : 999–1014
https://doi.org/10.3233/JAD-170351
79 P., Anand A. B., Kunnumakkara R. A. Newman B. Aggarwal (2007). Bioavailability of curcumin: problems and promises. Mol. Pharm., 4 : 807–818
https://doi.org/10.1021/mp700113r
80 F., Lo Cascio N., Puangmalai A., Ellsworth F., Bucchieri A., Pace A. Palumbo Piccionello (2019). Toxic tau oligomers modulated by novel curcumin derivatives. Sci. Rep., 9 : 19011
https://doi.org/10.1038/s41598-019-55419-w
81 R., Sato S., Vohra S., Yamamoto K., Suzuki K., Pavel S., Shulga Y. Blume (2020). Specific interactions between tau protein and curcumin derivatives: Molecular docking and ab initio molecular orbital simulations. J. Mol. Graph. Model., 98 : 107611
https://doi.org/10.1016/j.jmgm.2020.107611
82 M., Okuda I., Hijikuro Y., Fujita X., Wu S., Nakayama Y., Sakata Y., Noguchi M., Ogo S., Akasofu Y. Ito et al.. (2015). PE859, a novel tau aggregation inhibitor, reduces aggregated tau and prevents onset and progression of neural dysfunction in vivo. PLoS One, 10 : e0117511
https://doi.org/10.1371/journal.pone.0117511
83 M., Okuda I., Hijikuro Y., Fujita T., Teruya H., Kawakami T. Takahashi (2016). Design and synthesis of curcumin derivatives as tau and amyloid β dual aggregation inhibitors. Bioorg. Med. Chem. Lett., 26 : 5024–5028
https://doi.org/10.1016/j.bmcl.2016.08.092
84 W., Liu X., Hu L., Zhou Y., Tu S. Shi (2020). Orientation-inspired perspective on molecular inhibitor of tau aggregation by curcumin conjugated with ruthenium(ii) complex scaffold. J. Phys. Chem. B, 124 : 2343–2353
https://doi.org/10.1021/acs.jpcb.9b11705
85 K. C., Yu P., Kwan S. K. K., Cheung A. Ho (2018). Effects of resveratrol and morin on insoluble tau in tau transgenic mice. Transl. Neurosci., 9 : 54–60
https://doi.org/10.1515/tnsci-2018-0010
86 X. Y., Sun Q. X., Dong J., Zhu X., Sun L. F., Zhang M., Qiu X. L. Yu R. Liu (2019). Resveratrol rescues tau-induced cognitive deficits and neuropathology in a mouse model of tauopathy. Curr. Alzheimer Res., 16 : 710–722
https://doi.org/10.2174/1567205016666190801153751
87 G. M., Pasinetti J., Wang L., Ho W. Zhao (2015). Roles of resveratrol and other grape-derived polyphenols in Alzheimer’s disease prevention and treatment. Biochim. Biophys. Acta, 1852 : 1202–1208
https://doi.org/10.1016/j.bbadis.2014.10.006
88 A., Cornejo F., Aguilar Sandoval L., Caballero L., Machuca P., oz J., Caballero G., Perry A., Ardiles C. Areche (2017). Rosmarinic acid prevents fibrillization and diminishes vibrational modes associated to β sheet in tau protein linked to Alzheimer’s disease. J. Enzyme Inhib. Med. Chem., 32 : 945–953
https://doi.org/10.1080/14756366.2017.1347783
89 Y., Guo Y., Zhao Y., Nan X., Wang Y. Chen (2017). (‒)-Epigallocatechin-3-gallate ameliorates memory impairment and rescues the abnormal synaptic protein levels in the frontal cortex and hippocampus in a mouse model of Alzheimer’s disease. Neuroreport, 28 : 590–597
https://doi.org/10.1097/WNR.0000000000000803
90 S., Kumar V. G., Krishnakumar V., Morya S. Gupta (2019). Nanobiocatalyst facilitated aglycosidic quercetin as a potent inhibitor of tau protein aggregation. Int. J. Biol. Macromol., 138 : 168–180
https://doi.org/10.1016/j.ijbiomac.2019.07.081
91 S. K., Sonawane A. A., Balmik D., Boral S. Ramasamy (2019). Baicalein suppresses repeat tau fibrillization by sequestering oligomers. Arch. Biochem. Biophys., 675 : 108119
https://doi.org/10.1016/j.abb.2019.108119
92 M., Zhang Q., Wu X., Yao J., Zhao W., Zhong Q. Liu (2019). Xanthohumol inhibits tau protein aggregation and protects cells against tau aggregates. Food Funct., 10 : 7865–7874
https://doi.org/10.1039/C9FO02133G
93 M., Pickhardt Z., Gazova M., von Bergen I., Khlistunova Y., Wang A., Hascher E. Mandelkow J. Biernat (2005). Anthraquinones inhibit tau aggregation and dissolve Alzheimer’s paired helical filaments in vitro and in cells. J. Biol. Chem., 280 : 3628–3635
https://doi.org/10.1074/jbc.M410984200
94 E., Nepovimova E., Uliassi J., Korabecny L. E., a-Altamira S., Samez A., Pesaresi G. E., Garcia M., Bartolini V., Andrisano C. Bergamini et al.. (2014). Multitarget drug design strategy: quinone-tacrine hybrids designed to block amyloid-β aggregation and to exert anticholinesterase and antioxidant effects. J. Med. Chem., 57 : 8576–8589
https://doi.org/10.1021/jm5010804
95 A., Cornejo F., Salgado J., Caballero R., Vargas M. Simirgiotis (2016). Secondary metabolites in ramalina terebrata detected by UHPLC/ESI/MS/MS and identification of parietin as tau protein inhibitor. Int. J. Mol. Sci., 17 : 1303
https://doi.org/10.3390/ijms17081303
96 M., Frenkel-Pinter S., Tal R., Scherzer-Attali M., Abu-Hussien I., Alyagor T., Eisenbaum E., Gazit D. Segal (2016). Naphthoquinone-tryptophan hybrid inhibits aggregation of the tau-derived peptide PHF6 and reduces neurotoxicity. J. Alzheimers Dis., 51 : 165–178
https://doi.org/10.3233/JAD-150927
97 F., Salgado J., Caballero R., Vargas A. Cornejo (2020). Continental and antarctic lichens: isolation, identification and molecular modeling of the depside tenuiorin from the Antarctic lichen Umbilicaria antarctica as tau protein inhibitor. Nat. Prod. Res., 34 : 646–650
https://doi.org/10.1080/14786419.2018.1492576
98 C. J., Shi W., Peng J. H., Zhao H. L., Yang L. L., Qu C., Wang L. Y. Kong X. Wang (2020). Usnic acid derivatives as tau-aggregation and neuroinflammation inhibitors. Eur. J. Med. Chem., 187 : 111961
https://doi.org/10.1016/j.ejmech.2019.111961
99 N. V., Gorantla R., Das F. A., Mulani H. V. Thulasiram (2019). Neem derivatives inhibits tau aggregation. J. Alzheimers Dis. Rep., 3 : 169–178
https://doi.org/10.3233/ADR-190118
100 S., Xiao Q., Wu X., Yao J., Zhang W., Zhong J., Zhao Q. Liu (2021). Inhibitory effects of isobavachalcone on tau protein aggregation, tau phosphorylation, and oligomeric tau-induced apoptosis. ACS Chem. Neurosci., 12 : 123–132
https://doi.org/10.1021/acschemneuro.0c00617
101 S., Rafiee K., Asadollahi G., Riazi S. Ahmadian A. Saboury (2017). Vitamin B12 inhibits tau fibrillization via binding to cysteine residues of tau. ACS Chem. Neurosci., 8 : 2676–2682
https://doi.org/10.1021/acschemneuro.7b00230
102 S. Ghasemzadeh G. Riazi (2020). Inhibition of tau amyloid fibril formation by folic acid: In-vitro and theoretical studies. Int. J. Biol. Macromol., 154 : 1505–1516
https://doi.org/10.1016/j.ijbiomac.2019.11.032
103 L., Kifle D. Ortiz T. Shea (2009). Deprivation of folate and B12 increases neurodegeneration beyond that accompanying deprivation of either vitamin alone. J. Alzheimers Dis., 16 : 533–540
https://doi.org/10.3233/JAD-2009-1006
104 T., Dubey N. V., Gorantla K. T. Chandrashekara (2019). Photoexcited toluidine blue inhibits tau aggregation in Alzheimer’s disease. ACS Omega, 4 : 18793–18802
https://doi.org/10.1021/acsomega.9b02792
105 E., Haj, Y. Losev, V., Guru KrishnaKumar, E., Pichinuk, H., Engel, A., Raveh, E. Gazit. (2018) Integrating in vitro and in silico approaches to evaluate the “dual functionality” of palmatine chloride in inhibiting and disassembling tau-derived VQIVYK peptide fibrils. Biochim. Biophys. Acta Gen. Subj., 1862, 1565−1575
106 C. H., Lo C. K., Lim Z., Ding S. P., Wickramasinghe A. R., Braun K. H., Ashe E., Rhoades D. D. Thomas J. Sachs (2019). Targeting the ensemble of heterogeneous tau oligomers in cells: A novel small molecule screening platform for tauopathies. Alzheimers Dement., 15 : 1489–1502
https://doi.org/10.1016/j.jalz.2019.06.4954
107 M., Halliday H., Radford K. A. M., Zents C., Molloy J. A., Moreno N. C., Verity E., Smith C. A., Ortori D. A., Barrett M. Bushell et al.. (2017). Repurposed drugs targeting eIF2α-P-mediated translational repression prevent neurodegeneration in mice. Brain, 140 : 1768–1783
https://doi.org/10.1093/brain/awx074
108 A. L., La C. M., Walsh T. C., Neylan K. A., Vossel K., Yaffe A. D., Krystal B. L. Miller (2019). Long-term trazodone use and cognition: A potential therapeutic role for slow-wave sleep enhancers. J. Alzheimers Dis., 67 : 911–921
https://doi.org/10.3233/JAD-181145
109 P., Kumar H. Kalonia (2011). Novel protective mechanisms of antidepressants against 3-nitropropionic acid induced Huntington’s-like symptoms: a comparative study. J. Psychopharmacol., 25 : 1399–1411
https://doi.org/10.1177/0269881110364269
110 T. C., Grippe B. S. B., alves L. L., Louzada J. L., Quintas J. O. S., Naves E. F. Camargos O. brega (2015). Circadian rhythm in Alzheimer disease after trazodone use. Chronobiol. Int., 32 : 1311–1314
https://doi.org/10.3109/07420528.2015.1077855
111 V., Akbari S., Ghobadi S. Mohammadi (2020). The antidepressant drug; trazodone inhibits tau amyloidogenesis: Prospects for prophylaxis and treatment of AD. Arch. Biochem. Biophys., 679 : 108218
https://doi.org/10.1016/j.abb.2019.108218
112 R., Corpas V., valos D., Porquet P., a de Frutos S. M., Franciscato Cozzolino C. Sanfeliu B. Cardoso (2018). Melatonin induces mechanisms of brain resilience against neurodegeneration. J. Pineal Res., 65 : e12515
https://doi.org/10.1111/jpi.12515
113 A. A., Balmik, R., Das, A., Dangi, N. V., Gorantla, U. K. Marelli. (2020) Melatonin interacts with repeat domain of tau to mediate disaggregation of paired helical filaments. Biochim. Biophys. Acta, Gen. Subj., 1864, 129467
114 R., Das A. A. Balmik (2020). Effect of melatonin on tau aggregation and tau-mediated cell surface morphology. Int. J. Biol. Macromol., 152 : 30–39
https://doi.org/10.1016/j.ijbiomac.2020.01.296
115 S. C., Ren, Q. F., Suo, W. T., Du, H., Pan, M. M., Yang, R. H. Wang. (2010) Quercetin permeability across blood-brain barrier and its effect on the viability of U251 cells. Sichuan Da Xue Xue Bao Yi Xue Ban (in Chinese), 41, 751–754, 759
116 S. Habtemariam (2018). Molecular pharmacology of rosmarinic and salvianolic acids: Potential seeds for Alzheimer’s and vascular dementia drugs. Int. J. Mol. Sci., 19 : 458
https://doi.org/10.3390/ijms19020458
117 J., Wang C., Tang M. G., Ferruzzi B., Gong B. J., Song E. M., Janle T. Y., Chen B., Cooper M., Varghese A. Cheng et al.. (2013). Role of standardized grape polyphenol preparation as a novel treatment to improve synaptic plasticity through attenuation of features of metabolic syndrome in a mouse model. Mol. Nutr. Food Res., 57 : 2091–2102
https://doi.org/10.1002/mnfr.201300230
118 S., Rahmani L., Mogharizadeh F., Attar S. M., Rezayat S. E. Mousavi (2018). Probing the interaction of silver nanoparticles with tau protein and neuroblastoma cell line as nervous system models. J. Biomol. Struct. Dyn., 36 : 4057–4071
https://doi.org/10.1080/07391102.2017.1407673
119 M., Zaman E., Ahmad A., Qadeer G. Rabbani R. Khan (2014). Nanoparticles in relation to peptide and protein aggregation. Int J Nanomedicine, 9 : 899–912
120 L., Niu Y., Zou Y., Lin Y., Zheng Y. Yang (2019). Regulation mechanism of nanobiointerfaces in amyloid peptide assembly and aggregation structures. Sci. Sin. Chim., 49 : 500–515
https://doi.org/10.1360/N032018-00163
121 G., Hajsalimi S., Taheri F., Shahi F., Attar H. Ahmadi (2018). Interaction of iron nanoparticles with nervous system: an in vitro study. J. Biomol. Struct. Dyn., 36 : 928–937
https://doi.org/10.1080/07391102.2017.1302819
122 M. A., Vakilinezhad A., Amini H., Akbari Javar B. F., addini Beigi Zarandi H. Montaseri (2018). Nicotinamide loaded functionalized solid lipid nanoparticles improves cognition in Alzheimer’s disease animal model by reducing Tau hyperphosphorylation. Daru, 26 : 165–177
https://doi.org/10.1007/s40199-018-0221-5
123 S. K., Vimal H., Zuo Z., Wang H., Wang Z. Long (2020). Self-therapeutic nanoparticle that alters tau protein and ameliorates tauopathy toward a functional nanomedicine to tackle Alzheimer’s. Small, 16 : e1906861
https://doi.org/10.1002/smll.201906861
124 S. K., Sonawane A. Ahmad (2019). Protein-capped metal nanoparticles inhibit tau aggregation in Alzheimer’s disease. ACS Omega, 4 : 12833–12840
https://doi.org/10.1021/acsomega.9b01411
125 Y., Soeda M., Saito S., Maeda K., Ishida A., Nakamura S. Kojima (2019). Methylene blue inhibits formation of tau fibrils but not of granular tau oligomers: A plausible key to understanding failure of a clinical trial for Alzheimer’s disease. J. Alzheimers Dis., 68 : 1677–1686
https://doi.org/10.3233/JAD-181001
126 J., Zhao F., Yin L., Ji C., Wang C., Shi X., Liu H., Yang X. Wang (2020). Development of a tau-targeted drug delivery system using a multifunctional nanoscale metal-organic framework for Alzheimer’s disease therapy. ACS Appl. Mater. Interfaces, 12 : 44447–44458
https://doi.org/10.1021/acsami.0c11064
127 S. Manju (2011). Hollow microcapsules built by layer by layer assembly for the encapsulation and sustained release of curcumin. Colloids Surf. B Biointerfaces, 82 : 588–593
https://doi.org/10.1016/j.colsurfb.2010.10.021
128 X., Chen L. Q., Zou J., Niu W., Liu S. F. Peng C. Liu (2015). The stability, sustained release and cellular antioxidant activity of curcumin nanoliposomes. Molecules, 20 : 14293–14311
https://doi.org/10.3390/molecules200814293
129 S., Fan Y., Zheng X., Liu W., Fang X., Chen W., Liao X., Jing M., Lei E., Tao Q. Ma et al.. (2018). Curcumin-loaded PLGA-PEG nanoparticles conjugated with B6 peptide for potential use in Alzheimer’s disease. Drug Deliv., 25 : 1091–1102
https://doi.org/10.1080/10717544.2018.1461955
130 C., Gao X., Chu W., Gong J., Zheng X., Xie Y., Wang M., Yang Z., Li C. Gao (2020). Neuron tau-targeting biomimetic nanoparticles for curcumin delivery to delay progression of Alzheimer’s disease. J. Nanobiotechnology, 18 : 71
https://doi.org/10.1186/s12951-020-00626-1
131 Y., Hu X., Hu Y., Lu S., Shi D. Yang (2020). New strategy for reducing tau aggregation cytologically by a hairpinlike molecular inhibitor, tannic acid encapsulated in liposome. ACS Chem. Neurosci., 11 : 3623–3634
https://doi.org/10.1021/acschemneuro.0c00508
132 N. A., Singh V., Bhardwaj C., Ravi N., Ramesh A. K. A. Mandal Z. Khan (2018). EGCG nanoparticles attenuate aluminum chloride induced neurobehavioral deficits, beta amyloid and tau pathology in a rat model of Alzheimer’s disease. Front. Aging Neurosci., 10 : 244
https://doi.org/10.3389/fnagi.2018.00244
133 V., Armiento A. Spanopoulou (2020). Peptide-based molecular strategies to interfere with protein misfolding, aggregation, and cell degeneration. Angew. Chem. Int. Ed. Engl., 59 : 3372–3384
https://doi.org/10.1002/anie.201906908
134 S., Rauscher S., Baud M., Miao F. W. Keeley (2006). Proline and glycine control protein self-organization into elastomeric or amyloid fibrils. Structure, 14 : 1667–1676
https://doi.org/10.1016/j.str.2006.09.008
135 S. C., Li N. K., Goto K. A. Williams C. Deber (1996). Alpha-helical, but not β-sheet, propensity of proline is determined by peptide environment. Proc. Natl. Acad. Sci. USA., 93 : 6676–6681
https://doi.org/10.1073/pnas.93.13.6676
136 G., Pandey, S., Morla, S. Kumar. (2020) Modulation of tau protein aggregation using ‘Trojan’ sequences. Biochim. Biophys. Acta, Gen. Subj., 1864, 129569
137 I. H., Cheng K., Scearce-Levie J., Legleiter J. J., Palop H., Gerstein N., Bien-Ly J., li K. H., Ashe P. J. Muchowski et al.. (2007). Accelerating amyloid-beta fibrillization reduces oligomer levels and functional deficits in Alzheimer disease mouse models. J. Biol. Chem., 282 : 23818–23828
https://doi.org/10.1074/jbc.M701078200
138 C., Dammers D., Yolcu L., Kukuk D., Willbold M., Pickhardt E., Mandelkow A. H., Horn H., Sticht M. N., Malhis N. Will et al.. (2016). Selection and characterization of tau binding D-enantiomeric peptides with potential for therapy of Alzheimer disease. PLoS One, 11 : e0167432
https://doi.org/10.1371/journal.pone.0167432
139 N. V., Gorantla L. P., Sunny K., Rajasekhar P. G., Nagaraju P. P., Cg T. Govindaraju (2021). Amyloid-β-derived peptidomimetics inhibits tau aggregation. ACS Omega, 6 : 11131–11138
https://doi.org/10.1021/acsomega.9b03497
140 R. Best (2017). Computational and theoretical advances in studies of intrinsically disordered proteins. Curr. Opin. Struct. Biol., 42 : 147–154
https://doi.org/10.1016/j.sbi.2017.01.006
141 D. Meneksedag-Erol (2019). Atomistic simulation tools to study protein self-aggregation. Methods Mol. Biol., 2039 : 243–262
https://doi.org/10.1007/978-1-4939-9678-0_17
142 K. I., Popov K. A. T., Makepeace E. V., Petrotchenko N. V. Dokholyan C. Borchers (2019). Insight into the structure of the “unstructured” tau protein. Structure, 27 : 1710–1715.e4
https://doi.org/10.1016/j.str.2019.09.003
143 L., Larini M. M., Gessel N. E., LaPointe T. D., Do M. T., Bowers S. C. Feinstein J. Shea (2013). Initiation of assembly of tau (273‒284) and its ΔK280 mutant: an experimental and computational study. Phys. Chem. Chem. Phys., 15 : 8916–8928
https://doi.org/10.1039/c3cp00063j
144 V., Daebel S., Chinnathambi J., Biernat M., Schwalbe B., Habenstein A., Loquet E., Akoury K., Tepper H., ller M. Baldus et al.. (2012). β-Sheet core of tau paired helical filaments revealed by solid-state NMR. J. Am. Chem. Soc., 134 : 13982–13989
https://doi.org/10.1021/ja305470p
145 J., Adamcik A., nchez-Ferrer N., Ait-Bouziad N. P., Reynolds H. A. Lashuel (2016). Microtubule-binding R3 fragment from tau self-assembles into giant multistranded amyloid ribbons. Angew. Chem. Int. Ed. Engl., 55 : 618–622
https://doi.org/10.1002/anie.201508968
146 H., Liu H., Zhong Z., Xu Q., Zhang S. J. A., Shah H. Liu (2020). 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., 22 : 10968–10980
https://doi.org/10.1039/C9CP06954B
147 X., Li X., Dong G., Wei M., Margittai R. Nussinov (2018). The distinct structural preferences of tau protein repeat domains. Chem. Commun. (Camb.), 54 : 5700–5703
https://doi.org/10.1039/C8CC01263F
148 F. X., Smit J. A. Luiken P. Bolhuis (2017). Primary fibril nucleation of aggregation prone tau fragments PHF6 and PHF6*. J. Phys. Chem. B, 121 : 3250–3261
https://doi.org/10.1021/acs.jpcb.6b07045
149 H., Liu H., Zhong X., Liu S., Zhou S., Tan H. Liu (2019). 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., 10 : 4810–4823
https://doi.org/10.1021/acschemneuro.9b00488
150 N. A., Eschmann E. R., Georgieva P., Ganguly P. P., Borbat M. D., Rappaport Y., Akdogan J. H., Freed J. E. Shea (2017). Signature of an aggregation-prone conformation of tau. Sci. Rep., 7 : 44739
https://doi.org/10.1038/srep44739
151 J. P., Guo T., Arai J. Miklossy P. McGeer (2006). Abeta and tau form soluble complexes that may promote self aggregation of both into the insoluble forms observed in Alzheimer’s disease. Proc. Natl. Acad. Sci. USA, 103 : 1953–1958
https://doi.org/10.1073/pnas.0509386103
152 A. V., Rojas G. G. Maisuradze H. Scheraga (2018). Dependence of the formation of tau and Aβ peptide mixed aggregates on the secondary structure of the N-terminal region of Aβ. J. Phys. Chem. B, 122 : 7049–7056
https://doi.org/10.1021/acs.jpcb.8b04647
153 Y., Miller B. Ma (2011). Synergistic interactions between repeats in tau protein and Aβ amyloids may be responsible for accelerated aggregation via polymorphic states. Biochemistry, 50 : 5172–5181
https://doi.org/10.1021/bi200400u
154 T. D., Do N. J., Economou A., Chamas S. K., Buratto J. E. Shea M. Bowers (2014). Interactions between amyloid-β and Tau fragments promote aberrant aggregates: implications for amyloid toxicity. J. Phys. Chem. B, 118 : 11220–11230
https://doi.org/10.1021/jp506258g
155 W. S., Shin J., Di K. A., Murray C., Sun B., Li G. Bitan (2019). Different amyloid-beta self-assemblies have distinct effects on intracellular tau aggregation. Front. Mol. Neurosci., 12 : 268
https://doi.org/10.3389/fnmol.2019.00268
[1] Zongwei Guo, Fangkui Yin, Peiran Wang, Ting Song, Zhichao Zhang. Systems analysis of the “weights” of Bcl-2 and Mcl-1 in mitochondrial apoptosis pathway establishes a predictor for best drug combination ratio[J]. Quant. Biol., 2021, 9(3): 329-340.
[2] Cecylia S. Lupala, Xuanxuan Li, Jian Lei, Hong Chen, Jianxun Qi, Haiguang Liu, Xiao-Dong Su. Computational simulations reveal the binding dynamics between human ACE2 and the receptor binding domain of SARS-CoV-2 spike protein[J]. Quant. Biol., 2021, 9(1): 61-72.
[3] Jie Shi, Xiangrui Zeng, Rui Jiang, Tao Jiang, Min Xu. A simulated annealing approach for resolution guided homogeneous cryo-electron microscopy image selection[J]. Quant. Biol., 2020, 8(1): 51-63.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed