Advertisement

The Effect of The Neuroprotector Isatin on Complex Formation of Beta-Amyloid Peptide Fragments with Some Intracellular Proteins

  • O. A. Buneeva
  • O. V. Gnedenko
  • M. V. Medvedeva
  • A. S. Ivanov
  • A. E. MedvedevEmail author
Article
  • 7 Downloads

Abstract

Amyloid-β peptide (1−42) (Aβ1-42) is a key player in the development and progression of Alzheimer’s disease (AD) and related pathologies, determined by formation of protein aggregates in the central nervous system. Aβ1-42 binding to crucial intracellular targets (and their subsequent inactivation) obviously represents one of the earliest events preceding extracellular pathogenic oligomerization/aggregation of Aβ1-42. It is reasonable to expect that dissociation of the Aβ1-42 complexes with intracellular proteins by means of inhibitors followed by subsequent degradation of Aβ1-42 would not only protect critically important proteins but also prevent intracellular accumulation of Аβ1-42. The aim of this study was to investigate the effect of the neuroprotector isatin (100 µM) on interaction of known Aβ-binding proteins, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and pyruvate kinase, with Aβ1-42 and its fragments (Aβ1-28, Aβ12-28, Aβ25-35). Aβ1-42 and its fragments (Aβ1-28, Aβ12-28, Aβ25-35) immobilized on the Biacore optical biosensor chip interacted with GAPDH and pyruvate kinase. The lowest and basically equal Kd values were determined for GAPDH and pyruvate kinase complexes with immobilized Aβ1-42 and Aβ25-35. The presence of 100 µM isatin caused a significant (more than fivefold) increase in the Kd values for GAPDH complexes with all Aβ peptides except Aβ1-28. In contrast to GAPDH isatin increased dissociation of pyruvate kinase complexes only with Aβ1-42 (causing a 30-fold increase in Kd) and to a lesser extent with Aβ12-28 and Aβ25-35 (a 10-fold increase in the Kd value). It should be noted that in the presence of isatin the Kd values for GAPDH and pyruvate kinase complexes with all Aβ studied were in a narrower concentration range (10–7 M–10−6 M) than in the absence of this neuroprotector (10–8 M–10–6 M). Data obtained suggest existence of principal possibility of (pharmacological) protection of crucial intracellular targets against both Aβ1-42, and its aggressive truncated peptides (Aβ25-35).

Keywords

: beta-amyloid peptides Aβ1-42, Aβ1-28, Aβ12-28, Aβ25-35 amyloid-beta binding proteins isatin surface plasmon resonance optical biosensor Biacore 

Notes

REFERENCES

  1. 1.
    Hardy, J. and Selkoe, D.J., Science, 2002, vol. 297, pp. 353–356.CrossRefGoogle Scholar
  2. 2.
    Masters, C.L. and Selkoe. D.J., Cold Spring Harb. Perspect. Med., 2012, vol. 2, no. 6, a006262.CrossRefGoogle Scholar
  3. 3.
    Musiek, E.S. and Holtzman, D.M., Nat. Neurosci., 2015, vol. 18, pp. 800–806.CrossRefGoogle Scholar
  4. 4.
    LaFerla, F.M., Green, K.N., and Oddo, S., Nat. Rev. Neurosci., 2007, vol. 8, pp. 499–509.CrossRefGoogle Scholar
  5. 5.
    Kumar, S., Wirths, O., Theil, S., Gerth, J., Bayer, T.A., and Walter, J., Acta Neuropathol., 2013, vol. 125, pp. 699–709.CrossRefGoogle Scholar
  6. 6.
    Wirths, O., Multhaup, G., Czech, C., Blanchard, V., Moussaoui, S., Tremp, G., Pradier, L., Beyreuther, K., and Bayer, T.A., Neurosci. Lett., 2001, vol. 306, pp. 116–120.CrossRefGoogle Scholar
  7. 7.
    Reddy, P.H. and Beal, M.F., Trends. Mol. Med., 2008, vol. 14, pp. 45–53.CrossRefGoogle Scholar
  8. 8.
    Habib, L., Lee, M.T.C., and Yang, J., J. Biol. Chem., 2010, vol. 285, pp. 38 933–38 943.CrossRefGoogle Scholar
  9. 9.
    Yao, J., Du, H., Yan, S., Fang, F., Wang, C., Lue, L.F., Guo, L., Chen, D., Stern, D.M., Gunn Moore, F.J., Xi Chen, J., Arancio, O., and Yan, S.S., J. Neurosci., 2011, vol. 31, pp. 2313–2320.CrossRefGoogle Scholar
  10. 10.
    Petrushanko, I.Y., Mitkevich, V.A., Anashkina, A.A., Adzhubei, A.A., Burnysheva, K.M., Lakunina, V.A., Kamanina, Y.V., Dergousova, E.A., Lopina, O.D., Ogunshola, O.O., Bogdanova, A.Y., and Makarov, A.A., Sci. Rep., 2016, vol. 6, 27 738.CrossRefGoogle Scholar
  11. 11.
    Medvedev, A.E., Buneeva, O.A., and Glover, V., Biol. Targets Ther., 2007, vol. 1, pp. 151–162.Google Scholar
  12. 12.
    Medvedev, A., Buneeva, O., Gnedenko, O., Ershov, P., and Ivanov, A., Biofactors, 2018, vol. 44, no. 2, pp. 95–108.CrossRefGoogle Scholar
  13. 13.
    Medvedev, A.E., Buneeva, O.A., Kopylov, A.T., Gnedenko, O.V., Medvedeva, M.V., Kozin, S.A., Ivanov, A.S., Zgoda, V.G., and Makarov, A.A., Int. J. Mol. Sci., 2015, vol. 16, pp. 476–495.CrossRefGoogle Scholar
  14. 14.
    Florinskaya, A., Ershov, P., Mezentsev, Y., Kaluzhskiy, L., Yablokov, E., Medvedev, A., and Ivanov, A., Sensors (Basel), 2018, vol. 18, no. 5, pii: E1616.CrossRefGoogle Scholar
  15. 15.
    Buneeva, O.A., Gnedenko, O.V., Medvedeva, M.V., Ivanov, A.S., and Medvedev, A.E., Biomed. Khim., 2016, vol. 62, pp. 720–724.  https://doi.org/10.18097/PBMC20166206720 CrossRefGoogle Scholar
  16. 16.
    Scopes, R. K. and Stoter, A., Methods Enzymol., 1982, vol. 90, pt E, pp. 479–490.Google Scholar
  17. 17.
    Medvedev, A., Buneeva, O., Kopylov, A., Gne-denko, O., Ivanov, A., Zgoda, V., and Makarov, A.A., Methods Mol. Biol., 2015, vol. 1295, pp. 465–477.CrossRefGoogle Scholar
  18. 18.
    Rogeberg, M., Furlund, C.B., Moe, M.K., and Fladby, T., Biochimie, 2014, vol. 105, pp. 216–220.CrossRefGoogle Scholar
  19. 19.
    Millucci, L., Ghezzi, L., Bernardini, G., and Santucci, A., Current Protein and Peptide Science, 2010, vol. 11, pp. 54–67CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2019

Authors and Affiliations

  • O. A. Buneeva
    • 1
  • O. V. Gnedenko
    • 1
  • M. V. Medvedeva
    • 2
  • A. S. Ivanov
    • 1
  • A. E. Medvedev
    • 1
    Email author
  1. 1.Institute of Biomedical ChemistryMoscowRussia
  2. 2.Moscow State UniversityMoscowRussia

Personalised recommendations