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Neurochemical Journal

, Volume 12, Issue 4, pp 347–358 | Cite as

Effects and Mechanisms of Rapamycin Action on Experimental Neurodegeneration

  • A. B. Pupyshev
  • T. A. Korolenko
  • M. A. Tikhonova
Review Articles
  • 8 Downloads

Abstract

Rapamycin is a strong inducer of autophagy which binds with its target protein mTOR and causes inhibition of biosynthetic and mitotic cell activities. The review considers neuroprotective properties of autophagy induction by rapamycin. The most important feature of the neurodegenerative diseases is the accumulation of specific proteins, such as amyloid-β, α-synuclein, huntingtin, etc. Their accumulation is associated with the weakening of the cellular function of the protein quality control provided by the ubiquitin-proteasomal system and autophagy, including chaperone-mediated autophagy. In many cases, activation of autophagy by rapamycin is able to restore the quality control of proteins and organelles, to attenuate the accumulation of pathogenic proteins. Mechanisms of rapamycin therapeutic effects include activation of the clearance of neurons from pathogenic material and induction of both autophagosomal segregation of cellular material and the lysosomal flux by activating TFEB factor, which is the inductor of the lysosomal biogenesis. Short-term treatment with rapamycin has a positive therapeutic effect in models of acute brain injury (trauma, ischemia, hypoxia). Inhibition of neurodegeneration requires long-term therapy. Neuroprotective effect of rapamycin is higher if started at young age. Good results are achieved by prolonged treatment with rapamycin in intermittent mode.

Keywords

neurodegeneration neuroprotection autophagy rapamycin mTOR 

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References

  1. 1.
    Parkhit’ko, A.A., Favorova, O.O., Khabibullin, D.I., Anisimov, V.N., and Henske, E.P., Biokhimiya, 2014, vol. 79, no. 5, pp. 128–143.Google Scholar
  2. 2.
    Switon, K., Kotulska, K., Janusz-Kaminska, A., Zmorzynska, J., and Jaworski J., Neuroscience, 2017, vol. 341, pp. 112–153.CrossRefGoogle Scholar
  3. 3.
    Zoncu, R., Efeyan, A., and Sabatini, D. M., Nat. Rev. Mol. Cell Biol., 2011, vol. 12, no. 1, pp. 21–35.CrossRefGoogle Scholar
  4. 4.
    Wang, X., Pattison, J.S., and Su, H., Circ. Res., 2013, vol. 112, no. 2, pp. 367–381.CrossRefGoogle Scholar
  5. 5.
    Pupyshev, A.B., Korolenko, T.A., and Tikhonova, M.A., Neurosci. Behav. Physiol., 2017, vol. 47, no. 9, pp. 1109–1127.CrossRefGoogle Scholar
  6. 6.
    Dunlop, E.A. and Tee, A.R., Semin. Cell Dev. Biol., 2014, vol. 36, pp. 121–129.CrossRefGoogle Scholar
  7. 7.
    Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., and Mizushima, N., Nature, 2006, vol. 441, no. 7095, pp. 885–889.CrossRefGoogle Scholar
  8. 8.
    Rubinsztein, D.C., Shpilka, T., and Elazar, Z., Curr. Biol., 2012, vol. 22, no. 1, pp. R29–R34.CrossRefGoogle Scholar
  9. 9.
    Anding, A.L. and Baehrecke E.H., Curr. Top. Dev. Biol., 2015, vol. 14, no. 1, pp. 67–91.CrossRefGoogle Scholar
  10. 10.
    Yu, L., McPhee, C.K., Zheng, L., Mardones, G.A., Rong, Y., Peng, J., Mi, N., Zhao, Y., Liu, Z., Wan, F., Hailey, D.W., Oorschot, V., Klumperman, J., Baehrecke, E.H., and Lenardo, M.J., Nature, 2010, vol. 465, no. 7300, pp. 942–946.CrossRefGoogle Scholar
  11. 11.
    Juhász, G., Autophagy, 2012, vol. 8, no. 12, pp. 1875–1876.CrossRefGoogle Scholar
  12. 12.
    Mizushima, N., Yamamoto, A., Matsui, M., Yoshimori, T., and Ohsumi, Y., Mol. Biol. Cell, 2004, vol. 15, pp. 1101–1011.CrossRefGoogle Scholar
  13. 13.
    Codogno, P. and Meijer, A.J., Cell Death Differ., 2005, vol. 36, no. 12, pp. 1509–1518.CrossRefGoogle Scholar
  14. 14.
    O’Reilly, K.E., Rojo, F., She, Q.B., Solit, D., Mills, G.B., Smith, D., Lane, H., Hofmann, F., Hicklin, D.J., Ludwig, D.L., Baselga, J., and Rosen, N., Cancer Res., 2006, vol. 66, no. 3, pp. 1500–1508.CrossRefGoogle Scholar
  15. 15.
    Harrison, D.E., Strong, R., Sharp, Z.D., Nelson, J.F., Astle, C.M., Flurkey, K., Nadon, N.L., Wilkinson, J.E., Frenkel, K., Carter, C.S., Pahor, M., Javors, M.A., Fernandez, E., and Miller, RA., Nature, 2009, vol. 460, no. 7253, pp. 392–395.CrossRefGoogle Scholar
  16. 16.
    Bové, J., Martínez-Vicente, M., and Vila, M., Nat. Rev. Neurosci., 2011, vol. 12, no. 8, pp. 437–452.CrossRefGoogle Scholar
  17. 17.
    Menzies, F.M., Fleming, A., Caricasole, A., Bento, C.F., Andrews, S.P., Ashkenazi, A., Füllgrabe, J., Jackson, A., Jimenez-Sanchez, M., Karabiyik, C., Licitra, F., Lopez-Ramirez, A., Pavel, M., Puri, C., Renna, M., Ricketts, T., Schlotawa, L., Vicinanza, M., Won, H., Zhu, Y., Skidmore, J., and Rubinsztein, D.C., Neuron, 2017, vol. 93, no. 5, pp.1015–1034.CrossRefGoogle Scholar
  18. 18.
    Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E., and Tanaka, K., Nature, 2006, vol. 441, no. 7095, pp. 880–884.CrossRefGoogle Scholar
  19. 19.
    Kochergin, I.A. and Zakharova, M.N., Neirokhimiya, 2016, vol. 33, no. 1, pp. 12–24.Google Scholar
  20. 20.
    Carroll, B., Hewitt, G., and Korolchuk, V.I., Essays Biochem., 2013, vol. 55, pp. 119–131.CrossRefGoogle Scholar
  21. 21.
    Dehay, B., Bové, J., Rodríguez-Muela, N., Perier, C., Recasens, A., Boya, P., and Vila, M., J. Neurosci., 2010, vol. 30, no. 37, pp. 12535–12544.CrossRefGoogle Scholar
  22. 22.
    Vila, M., Bove, J., Dehay, B., Rodriguez-Muela, N., and Boya, P., Autophagy, 2011, vol. 7, no. 1, pp. 98–100.CrossRefGoogle Scholar
  23. 23.
    Caccamo, A., Majumder, S., Richardson, A., Strong, R., and Oddo, S., J. Biol. Chem., 2010, vol. 285, no. 17, pp. 13107–13120.CrossRefGoogle Scholar
  24. 24.
    Spilman, P., Podlutskaya, N., Hart, M.J., Debnath, J., Gorostiza, O., Bredesen, D., Richardson, A., Strong, R., and Galvan, V., PLoS One, 2010, vol. 5, p. e9979.CrossRefGoogle Scholar
  25. 25.
    Malagelada, C., Jin, Z.H., Jackson-Lewis, V., Przedborski, S., and Greene, L.A., J. Neurosci., 2010, vol. 30, no. 3, pp. 1166–1175.CrossRefGoogle Scholar
  26. 26.
    Liu, K., Shi, N., Sun, Y., Zhang, T., and Sun, X., Neurochem. Res., 2013, vol. 38, pp. 201–207.CrossRefGoogle Scholar
  27. 27.
    Spencer, B., Potkar, R., Trejo, M., Rockenstein, E., Patrick, C., Gindi, R., Adame, A., Wyss-Coray, T., and Masliah, E., J. Neurosci., 2009, vol. 29, no. 43, pp. 13578–13588.CrossRefGoogle Scholar
  28. 28.
    Bockaert, J. and Marin, P., Physiol. Rev., 2015, vol. 95, no. 4, pp. 1157–1187.CrossRefGoogle Scholar
  29. 29.
    Zhang, S., Salemi, J., Hou, H., Zhu, Y., Mori, T., Giunta, B., Obregon, D., and Tan, J., Biochem. Biophys. Res. Commun., 2010, vol. 398, no. 3, pp. 337–341.CrossRefGoogle Scholar
  30. 30.
    Malagelada, C., Jin, Z.H., and Greene, L.A., J. Neurosci., 2008, vol. 28, no. 53, pp. 14363–14371.CrossRefGoogle Scholar
  31. 31.
    Kim, S.R., Chen, X., Oo, T.F., Kareva, T., Yarygina, O., Wang, C., During, M., Kholodilov, N., and Burke, R.E., Ann. Neurol., 2011, vol. 70, no. 1, pp. 110–120.CrossRefGoogle Scholar
  32. 32.
    Domanskyi, A., Geissler, C., Vinnikov, I.A., Alter, H., Schober, A., Vogt, M.A., Gass, P., Parlato, R., and Schütz, G., FASEB J., 2011, vol. 25, no. 9, pp. 2898–2910.CrossRefGoogle Scholar
  33. 33.
    Nixon, R.A., Wegiel, J., Kumar, A., Yu, W.H., Peterhoff, C., Cataldo, A., and Cuervo, A.M., J. Neuropathol. Exp. Neurol., 2005, vol. 64, no. 2, pp. 113–122.CrossRefGoogle Scholar
  34. 34.
    Boland, B., Kumar, A., Lee, S., Platt, F.M., Wegiel, J., Yu, W.H., and Nixon, R.A., J. Neurosci., 2008, vol. 28, no. 27, pp. 6926–6937.CrossRefGoogle Scholar
  35. 35.
    Crews, L., Spencer, B., Desplats, P., Patrick, C., Paulino, A., Rockenstein, E., Hansen, L., Adame, A., Galasko, D., and Masliah, E., PLoS One, 2010, vol. 5, p. e9313.CrossRefGoogle Scholar
  36. 36.
    Perier, C., Bové, J., Wu, D.C., Dehay, B., Choi, D.K., Jackson-Lewis, V., Rathke-Hartlieb, S., Bouillet, P., Strasser, A., Schulz, J.B., and Przedborski, S., and Vila, M., Proc. Natl. Acad. Sci. U. S. A., 2007, vol. 104, no. 19, pp. 8161–8166.CrossRefGoogle Scholar
  37. 37.
    Pan, T., Kondo, S., Zhu, W., Xie, W., Jankovic, J., and Le, W., Neurobiol. Dis., 2008, vol. 32, no. 1, pp. 16–25.CrossRefGoogle Scholar
  38. 38.
    Martini-Stoica, H., Xu, Y., Ballabio, A., and Zheng, H., Trends Neurosci., 2016, vol. 39, no. 4, pp. 221–234.CrossRefGoogle Scholar
  39. 39.
    Decressac, M., Mattsson, B., Weikop, P., Lundblad, M., Jakobsson, J., and Bjorklund, A., Proc. Natl. Acad. Sci. U. S. A., 2013, vol. 110, no. 19, pp. E1817–E1826.CrossRefGoogle Scholar
  40. 40.
    Polito, V.A., Li, H., Martini-Stoica, H., Wang, B., Yang, L., Xu, Y., Swartzlander, D.B., Palmieri, M., di Ronza, A., Lee, V.M., Sardiello, M., Ballabio, A., and Zheng, H., EMBO Mol. Med., 2014, vol. 6, no. 9, pp. 1142–1160.CrossRefGoogle Scholar
  41. 41.
    Cullen, V., Lindfors, M., Ng, J., Paetau, A., Swinton, E., Kolodziej, P., Boston, H., Saftig, P., Woulfe, J., Feany, M.B., Myllykangas, L., Schlossmacher, M.G., and Tyynelä, J., Mol. Brain, 2009, vol. 2, p. 5. doi 10.1186/1756-6606-2-5CrossRefGoogle Scholar
  42. 42.
    King, M.A., Hands, S., Hafiz, F., Mizushima, N., Tolkovsky, A.M., and Wyttenbach, A., Mol. Pharmacol., 2008, vol. 73, no. 4, pp. 1052–1063.CrossRefGoogle Scholar
  43. 43.
    Tanemura, M., Ohmura, Y., Deguchi, T., Machida, T., Tsukamoto, R., Wada, H., Kobayashi, S., Marubashi, S., Eguchi, H., Ito, T., Nagano, H., Mori, M., and Doki, Y., Am. J. Transplant., 2012, vol. 12, no. 1, pp. 102–114.CrossRefGoogle Scholar
  44. 44.
    Hernandez, D., Torres, C.A., Setlik, W., Cebrian, C., Mosharov, E.V., Tang, G., Cheng, H.C., Kholodilov, N., Yarygina, O., Burke, R.E., Gershon, M., and Sulzer, D., Neuron, 2012, vol. 74, pp. 277–284.CrossRefGoogle Scholar
  45. 45.
    Kwon, C.H., Zhu, X., Zhang, J., and Baker, S.J., Proc. Natl. Acad. Sci. U. S. A., 2003, vol. 100, no. 22, pp. 12923–12928.CrossRefGoogle Scholar
  46. 46.
    Zhu, G. and Baker, S.J., Methods Mol. Biol., 2016, vol. 1388, pp. 53–62.CrossRefGoogle Scholar
  47. 47.
    Erlich, S., Alexandrovich, A., Shohami, E., and Pinkas-Kramarski, R., Neurobiol. Dis., 2007, vol. 26, no. 1, pp. 86–93.CrossRefGoogle Scholar
  48. 48.
    Srivastava, I.N., Shperdheja, J., Baybis, M., Ferguson, T., and Crino, P.B., Neurobiol. Dis., 2016, vol. 85, pp. 144–154.CrossRefGoogle Scholar
  49. 49.
    Fang, Y., Westbrook, R., Hill, C., Boparai, R.K., Arum, O., Spong, A., Wang, F., Javors, M.A., Chen, J., Sun, L.Y., and Bartke, A., Cell Metab., 2013, vol. 17, no. 3, pp. 456–462.CrossRefGoogle Scholar
  50. 50.
    Kurdi, A., De Doncker, M., Leloup, A., Neels, H., Timmermans, J.P., Lemmens, K., Apers, S., De Meyer, G.R.Y., and Martinet, W., Br. J. Pharmacol., 2016, vol. 173, no. 23, pp. 3359–3371.CrossRefGoogle Scholar
  51. 51.
    Ozcelik, S., Fraser, G., Castets, P., Schaeffer, V., Skachokova, Z., Breu, K., Clavaguera, F., Sinnreich, M., Kappos, L., Goedert, M., Tolnay, M., and Winkler, D.T., PLoS One, 2013, vol. 8, p. e62459.CrossRefGoogle Scholar
  52. 52.
    Bai, X., Wey, M.C., Fernandez, E., Hart, M.J., Gelfond, J., Bokov, A.F., Rani, S., and Strong, R., Pathobiol. Age-Relat. Dis., 2015, vol. 5, p. 28743.CrossRefGoogle Scholar
  53. 53.
    Majumder, S., Richardson, A., Strong, R., and Oddo, S., PLoS One, 2011, vol. 6, p. e25416.CrossRefGoogle Scholar
  54. 54.
    Pierce, A., Podlutskaya, N., Halloran, J.J., Hussong, S.A., Lin, P.Y., Burbank, R., Hart, M.J., and Galvan, V., J. Neurochem., 2013, vol. 124, no. 6, pp. 880–893.CrossRefGoogle Scholar
  55. 55.
    Lin, A.L., Zheng, W., Halloran, J.J., Burbank, R.R., Hussong, S.A., Hart, M.J., Javors, M., Shih, Y.Y., Muir, E., Solano Fonseca, R., Strong, R., Richardson, A.G., Lechleiter, J.D., Fox, P.T., and Galvan, V., J. Cereb. Blood Flow Metab., 2013, vol. 33, no. 9, pp. 1412–1421.CrossRefGoogle Scholar
  56. 56.
    Cortes, C.J., Qin, K., Cook, J., Solanki, A., and Mastrianni, J.A., J. Neurosci., 2012, vol. 32, no. 36, pp. 12396–12405.CrossRefGoogle Scholar
  57. 57.
    Menzies, F.M., Huebener, J., Renna, M., Bonin, M., Riess, O., and Rubinsztein, D.C., Brain, 2010, vol. 133, pp. 93–104.CrossRefGoogle Scholar
  58. 58.
    Jiang, T., Yu, J.T., Zhu, X.C., Tan, M.S., Wang, H.F., Cao, L., Zhang, Q.Q., Shi, J.Q., Gao, L., Qin, H., Zhang, Y.D., and Tan, L., Pharmacol. Res., 2014, vol. 81, pp. 54–63.CrossRefGoogle Scholar
  59. 59.
    Jiang, T., Yu, J.T., Zhu, X.C., Zhang, Q.Q., Cao, L., Wang, H.F., Tan, M.S., Gao, Q., Qin, H., Zhang, Y.D., and Tan, L. Neuropharmacology, 2014, vol. 85, pp. 121–130.CrossRefGoogle Scholar
  60. 60.
    González-Polo, R.A., Pizarro-Estrella, E., Yakhine-Diop, S.M., Rodríguez-Arribas, M., Gómez-Sánchez, R., Pedro, J.M., and Fuentes, J.M., Curr. Top. Med. Chem., 2015, vol. 15, no. 21, pp. 2152–2174.CrossRefGoogle Scholar
  61. 61.
    Yang, D.S., Stavrides, P., Mohan, P.S., Kaushik, S., Kumar, A., Ohno, M., Schmidt, S.D., Wesson, D., Bandyopadhyay, U., Jiang, Y., Pawlik, M., Peterhoff, C.M., Yang, A.J., Wilson, D.A., St. George-Hyslop, P., Westaway, D., Mathews, P.M., Levy, E., Cuervo, A.M., and Nixon, R.A., Brain, 2011, vol. 134, pp. 258–277.CrossRefGoogle Scholar
  62. 62.
    Martinez-Vicente, M., Talloczy, Z., Wong, E., Tang, G., Koga, H., Kaushik, S., de Vries, R., Arias, E., Harris, S., Sulzer, D., and Cuervo, A.M., Nat. Neurosci., 2010, vol. 13, no. 5, pp. 567–576.CrossRefGoogle Scholar
  63. 63.
    Duarte-Silva, S., Silva-Fernandes, A., Neves-Carvalho, A., Soares-Cunha, C., Teixeira-Castro, A., and Maciel, P., Neuroscience, 2016, vol. 313, pp. 162–173.CrossRefGoogle Scholar
  64. 64.
    Santini, E., Heiman, M., Greengard, P., Valjent, E., and Fisone, G., Sci. Signaling, 2009, vol. 2, no. 80, p. ra36.CrossRefGoogle Scholar
  65. 65.
    Meng, Y., Yong, Y., Yang, G., Ding, H., Fan, Z., Tang, Y., Luo, J., and Ke, Z.J., J. Neurochem., 2013, vol. 126, pp. 805–818.CrossRefGoogle Scholar
  66. 66.
    Viscomi, M.T., D’Amelio, M., Cavallucci, V., Latini, L., Bisicchia, E., Nazio, F., Fanelli, F., Maccarrone, M., Moreno, S., Cecconi, F., and Molinari, M., Autophagy, 2012, vol. 8, pp. 222–235.CrossRefGoogle Scholar
  67. 67.
    Qi, H., Su, F.Y., Wan, S., Chen, Y., Cheng, Y.Q., and Liu, A.J., CNS Neurosci. Ther., 2014, vol. 20, pp. 991–998.CrossRefGoogle Scholar
  68. 68.
    Ravikumar, B., Vacher, C., Berger, Z., Davies, J.E., Luo, S., Oroz, L.G., Scaravilli, F., Easton, D.F., Duden, R., O’Kane, C.J., and Rubinsztein, D.C., Nat. Genet., 2004, vol. 36., pp. 585–595.CrossRefGoogle Scholar
  69. 69.
    Caccamo, A., Magrì, A., Medina, D.X., Wisely, E.V., López-Aranda, M.F., Silva, A.J., and Oddo, S., Aging Cell, 2013, vol. 12, pp. 370–380.CrossRefGoogle Scholar
  70. 70.
    Zhang, X., Li, L., Chen, S., Yang, D., Wang, Y., Zhang, X., Wang, Z., and Le, W., Autophagy, 2011, vol. 7, pp. 412–425.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  • A. B. Pupyshev
    • 1
    • 3
  • T. A. Korolenko
    • 1
  • M. A. Tikhonova
    • 1
    • 2
  1. 1.Scientific Research Institute of Physiology and Basic MedicineNovosibirskRussia
  2. 2.Novosibirsk State UniversityNovosibirskRussia
  3. 3.NovosibirskRussia

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