Journal of the Iranian Chemical Society

, Volume 16, Issue 1, pp 33–44 | Cite as

Diverse antithetical effects of the bio-compatible Ag-NPs on the hen egg lysozyme amyloid aggregation: from an efficient inhibitor to obscure inducer

  • Hassan RamshiniEmail author
  • Azam-Sadat Moghaddasi
  • Nasrin Mollania
  • Reza KhodarahmiEmail author
Original Paper


Formation and deposition of amyloid aggregates are pathological hallmark of several neurodegenerative diseases such as Alzheimer’s (AD), Parkinson (PD), and Huntington’s diseases. Thus, one therapeutic strategy is to eliminate/dismantle toxic aggregates by suppressing/breaking fibrils. The conventional treatment strategies often fail due to their poor solubility, lower bioavailability, and ineffective ability to cross the blood–brain barrier. Nanoparticles (NPs) exhibit promise at low sub-stoichiometric ratios, and, due to tunable size and surface properties, present an ideal platform for the design of effective aggregation suppressors. In the present study, we characterized the bio-compatible (silver nanoparticles) Ag-NPs and assessed those antithetical aggregation inhibitory/inductive capabilities at different NPs/protein ratios. It is proposed that negative (inhibitory) and positive (inductive) influences of NPs on the hen egg white lysozyme (HEWL) amyloid aggregation are achieved via different independent mechanisms. Based on obtained insights in this field, rationally design of effective NP-based therapeutics for neurodegenerative diseases may be a feasible perspective.

Graphical abstract


Amyloid aggregation Lysozyme Inhibition Silver nanoparticles 



This work was supported by a grant from the research council of the University of Payam Noor (54093). Valuable assistances provided by Mr. Sajjad Esmaeili are greatly appreciated.


  1. 1.
    M. Zaman, E. Ahmad, A. Qadeer, G. Rabbani, R.H. Khan, Int. J. Nanomed. 9, 899 (2014)Google Scholar
  2. 2.
    R. Parveen, T.N. Shamsi, S. Fatima, Int. J. Biol. Macromol. 94, 386 (2017)CrossRefGoogle Scholar
  3. 3.
    W.H. De Jong, P.J. Borm, Int. J. Nanomed. 3, 133 (2008)CrossRefGoogle Scholar
  4. 4.
    L. Crombez, M.C. Morris, S. Deshayes, F. Heitz, G. Divita, Curr. Pharm. Des. 14, 3656 (2008)CrossRefGoogle Scholar
  5. 5.
    L. Gao, J. Zhuang, L. Nie, J. Zhang, Y. Zhang, N. Gu, T. Wang, J. Feng, D. Yang, S. Perrett, X. Yan, Nat. Nanotechnol. 2, 577 (2007)CrossRefGoogle Scholar
  6. 6.
    P.M. Heegaard, U. Boas, D.E. Otzen, Macromol. Biosci. 7, 1047 (2007)CrossRefGoogle Scholar
  7. 7.
    E. Casals, T. Pfaller, A. Duschl, G.J. Oostingh, V. Puntes, ACS Nano 4, 3623 (2010)CrossRefGoogle Scholar
  8. 8.
    T. Cedervall, I. Lynch, M. Foy, T. Berggad, S. Donnelly, G. Cagney, S. Linse, K. Dawson, Angew. Chem. Int. Ed. 46, 5754 (2007)CrossRefGoogle Scholar
  9. 9.
    A.A. Vertegel, R.W. Siegel, J.S. Dordick, Langmuir 20, 6800 (2004)CrossRefGoogle Scholar
  10. 10.
    W. Shang, J.H. Nuffer, J.S. Dordick, R.W. Siegel, Nano Lett. 7, 1991 (2007)CrossRefGoogle Scholar
  11. 11.
    X. Wu, G. Narsimhan, Langmuir 24, 4989 (2008)CrossRefGoogle Scholar
  12. 12.
    L. Fei, S. Perrett, Int. J. Mol. Sci. 10, 646 (2009)CrossRefGoogle Scholar
  13. 13.
    K. Akiyoshi, Y. Sasaki, J. Sunamoto, Bioconjug. Chem. 10, 321 (1999)CrossRefGoogle Scholar
  14. 14.
    M. De, V.M. Rotello, Chem. Commun. Camb. 14, 3504 (2008)CrossRefGoogle Scholar
  15. 15.
    T.P.J. Knowles, M. Vendruscolo, C.M. Dobson, Nat. Rev. Mol. Cell Biol 15, 496 (2014)CrossRefGoogle Scholar
  16. 16.
    C.A. Ross, M.A. Poirier, Nat. Med. 10, 510 (2004)CrossRefGoogle Scholar
  17. 17.
    C. Haass, D.J. Selkoe, Nat. Rev. Mol. Cell. Bio. 8, 101 (2007)CrossRefGoogle Scholar
  18. 18.
    F. Gervais, J. Paquette, C. Morissette, P. Krzywkowski, M. Yu, Neurobiol Aging 28, 537 (2007)CrossRefGoogle Scholar
  19. 19.
    S. Salomone, F. Caraci, G.M. Leggio, J. Fedotova, F. Drago, Br. J. ClinPharmacol. 73, 504 (2012)Google Scholar
  20. 20.
    R. Alyautdin, I. Khalin, M.I. Nafeeza, M.H. Haron, D. Kuznetsov, Int. J. Nanomedicine 9, 795 (2014)Google Scholar
  21. 21.
    S. Stegemann, F. Leveiller, D. Franchi, H. de Jong, H. Lindén, Eur. J. Pharm. Sci. 31, 249 (2007)CrossRefGoogle Scholar
  22. 22.
    D. Paolino, D. Cosco, R. Molinaro, C. Celia, M. Fresta, Drug Discov. Today 16, 311 (2011)CrossRefGoogle Scholar
  23. 23.
    S. Singh, M. Singh, I.S. Gambhir, Dig. J. Nanomater. Biostruct. 3, 75 (2008)Google Scholar
  24. 24.
    V. Bellotti, M. Nuvolone, S. Giorgetti, L. Obici, G. Palladini, P. Russo, F. Lavatelli, V. Perfetti, G. Merlini, Ann. Med. 39, 200 (2007)CrossRefGoogle Scholar
  25. 25.
    D. Chopra, M. Gulati, V. Saluja, P. Pathak, P. Bansal, Recent Pat. CNS Drug Discov. 3, 216 (2008)Google Scholar
  26. 26.
    M.A. Busquets, R. Sabaté, J. Estelrich, Nanoscale Res Lett. 9, 538 (2014)CrossRefGoogle Scholar
  27. 27.
    C. Wang, M. Zhang, X. Mao, Y. Yu, C.X. Wang, Y.L. Yang, Adv. Mater. 25, 3780 (2013)CrossRefGoogle Scholar
  28. 28.
    Y.A. Krutyakov, A.A. Kudrynskiy, A.Y. Olenin, G.V. Lisichkin, Russ. Chem. Rev. 77, 233Google Scholar
  29. 29.
  30. 30.
    J.H. Lee, Y.S. Kim, K.S. Song, H.R. Ryu, J.H. Sung, J.D. Park, H.M. Park, N.W. Song, B.S. Shin, D. Marshak, K. Ahn, J.E. Lee, I. Yu, FibreToxicol. 10, 36 (2013)Google Scholar
  31. 31.
    W.J. Trickler, S.M. Lantz, R.C. Murdock, A.M. Schrand, B.L. Robinson, G.D. Newport, J.J. Schlager, S.J. Oldenburg, M.G. Paule, W. Slikker Jr.. S.M. Hussain, S.F. Ali, Toxicol. Sci. 118, 160 (2010)CrossRefGoogle Scholar
  32. 32.
    M. Mahmoudi, H.R. Kalhor, S. Laurent, I. Lynch, Nanoscale 5, 2570 (2013)CrossRefGoogle Scholar
  33. 33.
    H. Ramshini, A.S. Moghaddasi, L.S. Aldaghi, N. Mollania, A. Ebrahim-Habibi, Arch. Ital. Biol. 155, 131–141 (2017)Google Scholar
  34. 34.
    L.A. Morozova-Roche, J. Zurdo, A. Spencer, W. Noppe, V. Receveur, D.B. Archer, M. Joniau, C.M. Dobson, J. Struct. Biol. 130, 339 (2000)CrossRefGoogle Scholar
  35. 35.
    A. Cao, D. Hu, L. Lai, Formation of amyloid fibrils from fully reduced hen egg white lysozyme. Protein Sci. 13, 319 (2004)CrossRefGoogle Scholar
  36. 36.
    H. Ramshini, B. Mannini, K. Khodayari, A. Ebrahim-Habibi, A.S. Moghaddasi, R. Tayebee, F. Chiti,Eur. J. Med. Chem. 124, 361 (2016)CrossRefGoogle Scholar
  37. 37.
    R. Swaminathan, V.K. Ravi, S. Kumar, M.V. Kumar, N. Chandra, Adv. Protein Chem. Struct. Biol. 84, 63 (2011)CrossRefGoogle Scholar
  38. 38.
    M. Xu, V.A. Shashilov, V.V. Ermolenkov, L. Fredriksen, D. Zagorevski, I.K. Lednev, Protein Sci. 16, 815 (2007)CrossRefGoogle Scholar
  39. 39.
    A.J. Sophianopoulos, C. Rhodes, D.N. Holcomb, K.E. Van Holde, J. Biol. Chem. 237, 1107 (1962)Google Scholar
  40. 40.
    M.R. Nilsson, Methods 34, 151 (2004)CrossRefGoogle Scholar
  41. 41.
    A. Jangholi, M.R. Ashrafi-Kooshk, S.S. Arab, G. Riazi, F. Mokhtari, M. Poorebrahim, H. Mahdiuni, B.I. Kurganov, A.A. Moosavi-Movahedi, R. Khodarahmi, Arch. Biochem. Biophys. 609, 1 (2016)CrossRefGoogle Scholar
  42. 42.
    N. Rezaei-Ghaleh, H. Ramshini, A. Ebrahim-Habibi, A.A. Moosavi-Movahedi, M. Nemat-Gorgani, Biophys. Chem. 132, 23 (2008)CrossRefGoogle Scholar
  43. 43.
    A. Mishra, D.K. Mishra, N.K. Bohra, Annal. Arid Zone 54(1), 2), 43 (2015)Google Scholar
  44. 44.
    K. Jyoti, M. Baunthiyal, A. Singh, J Radiat. Res. App. Sci. 9, 217 (2016)CrossRefGoogle Scholar
  45. 45.
    S. Roy, T. Mukherjee, S. Chakraborty, T.K. Das, Dig. J. Nanomater. Biostruct. 8, 197 (2013)Google Scholar
  46. 46.
    M. Dehvari, A. Ghahghaei, Int. J. Biol. Macromol. 108, 1128 (2018)CrossRefGoogle Scholar
  47. 47.
    S. Mayilo, M.A. Kloster, M. Wunderlich, A. Lutich, T.A. Klar, A. Nichtl, K. Kùrzinger, F.D. Stefani, J. Feldmann, Nano Lett. 9, 4558 (2009)CrossRefGoogle Scholar
  48. 48.
    C.C. Lee, A. Nayak, A. Sethuraman, G. Belfort, G.J. McRae, A three-Stage Kinetic Model of Amyloid Fibrillation. Biophys. J. 92, 3448 (2007)CrossRefGoogle Scholar
  49. 49.
    F. Chiti, C.M. Dobson, Annu. Rev. Biochem. 75, 333 (2006)CrossRefGoogle Scholar
  50. 50.
    J.T. Jarrett, P.T. Lansbury, Biochemistry 31, 12345 (1992)CrossRefGoogle Scholar
  51. 51.
    R. Khodarahmi, H. Soori, M. Amani, Protein. J. 28, 349 (2009)CrossRefGoogle Scholar
  52. 52.
    C. Cabaleiro-Lago, F. Quinlan-Pluck, I. Lynch, S. Lindman, A.M. Minogue, E. Thulin, D.M. Walsh, K.A. Dawson, S. Linse, Am. Chem. Soc. 130, 15437 (2008)CrossRefGoogle Scholar
  53. 53.
    S.C. McBain, H.H. Yiu, J. Dobson, Magnetic nanoparticles for gene and drugdelivery. Int. J. Nanomed. 3, 169 (2008)Google Scholar
  54. 54.
    S. Radic, T.P. Davis, P.C. Ke, F. Ding, RSC Adv. 5, 105489 (2015)CrossRefGoogle Scholar
  55. 55.
    S. Linse, C. Cabaleiro-Lago, W.F. Xue, I. Lynch, S. Lindman, E. Thulin, S.E. Radford, K.A. Dawson, Proc. Natl. Acad. Sci. USA, 104, 8691 (2007)CrossRefGoogle Scholar
  56. 56.
    T. Mosmann, J. Immunol. Methods 65, 55 (1983)CrossRefGoogle Scholar
  57. 57.
    H. Ramshini, M. mohammad-zadeh, A. Ebrahim-Habibi. Int. J. Biol. Macromol. 78, 396 (2015)CrossRefGoogle Scholar
  58. 58.
    A.A. Ladiwala, J.S. Dordick, P.M. Tessier, J. Biol. Chem. 286, 3209 (2011)CrossRefGoogle Scholar
  59. 59.
    S.S. Shahangian, B. Rasti, R.H. Sajedi, R. Khodarahmi, M. Taghdir, B. Ranjbar, Protein. J. 30, 549 (2011)CrossRefGoogle Scholar
  60. 60.
    X. Zhang, X. Fu, H. Zhang, C. Liu, W. Jiao, Z. Chang, Int. J. Biochem. Cell Biol. 37, 1232 (2005)CrossRefGoogle Scholar
  61. 61.
    R. Khodarahmi, M. Beyrami, H. Soori, Arch. Biochem. Biophys. 477, 67 (2008)CrossRefGoogle Scholar
  62. 62.
    A. Nitani, H. Muta, M. Adachi, M. So, K. Sasahara, K. Sakurai, E. Chatani, K. Naoe, H. Ogi, D. Hall, Y.Goto, J. Biol. Chem. 292, 21219 (2017)CrossRefGoogle Scholar
  63. 63.
    G. Wei, Z. Su, N.P. Reynolds, P. Arosio, I.W. Hamley, E. Gazit, R. Mezzenga, Chem. Soc. Rev. 46, 4661 (2017)CrossRefGoogle Scholar

Copyright information

© Iranian Chemical Society 2018

Authors and Affiliations

  1. 1.Biology DepartmentPayam Noor UniversityTehranIslamic Republic of Iran
  2. 2.Department of Biology, Faculty of Basic SciencesHakim Sabzevari UniversitySabzevarIran
  3. 3.Medical Biology Research CenterKermanshah University of Medical SciencesKermanshahIran

Personalised recommendations