Immunoproteasome Inhibitor ONX-0914 Affects Long-Term Potentiation in Murine Hippocampus

This is a preview of subscription content, access via your institution.

Fig. 1

Data availability

(Data transparency) Data is available upon request.

References

  1. Bhattarai D, Lee MJ, Baek A, Yeo IJ, Miller Z, Baek YM, Lee S, Kim DE, Hong JT, Kim KB (2020) LMP2 inhibitors as a potential treatment for Alzheimer's disease. J Med Chem 63(7):3763–3783. https://doi.org/10.1021/acs.jmedchem.0c00416

    CAS  Article  PubMed  Google Scholar 

  2. de Bruin G, Huber EM, Xin BT, van Rooden EJ, Al-Ayed K, Kim KB, Kisselev AF, Driessen C, van der Stelt M, van der Marel GA, Groll M, Overkleeft HS (2014) Structure-based design of β1i or β5i specific inhibitors of human immunoproteasomes. J Med Chem 57(14):6197–6209. https://doi.org/10.1021/jm500716s

    CAS  Article  PubMed  Google Scholar 

  3. Díaz-Hernández M, Hernández F, Martín-Aparicio E, Gómez-Ramos P, Morán MA, Castaño JG, Ferrer I, Avila J, Lucas JJ (2003) Neuronal induction of the immunoproteasome in Huntington's disease. J Neurosci 23(37):11653–11661. https://doi.org/10.1523/JNEUROSCI.23-37-11653.2003

    Article  PubMed  PubMed Central  Google Scholar 

  4. Fonseca R, Vabulas RM, Hartl FU, Bonhoeffer T, Nägerl UV (2006) A balance of protein synthesis and proteasome-dependent degradation determines the maintenance of LTP. Neuron. 52(2):239–245. https://doi.org/10.1016/j.neuron.2006.08.015

    CAS  Article  PubMed  Google Scholar 

  5. Funikov SY, Spasskaya DS, Burov AV, Teterina EV, Ustyugov AA, Karpov VL, Morozov AV (2020) The number of proteasome gene transcripts differs between parts of the mouse central nervous system. Molecular Biology 54(6):1–10. https://doi.org/10.31857/S002689842006004X in press

    Article  Google Scholar 

  6. Gavilán MP, Castaño A, Torres M, Portavella M, Caballero C, Jiménez S, García-Martínez A, Parrado J, Vitorica J, Ruano D (2009) Age-related increase in the immunoproteasome content in rat hippocampus: molecular and functional aspects. J Neurochem 108(1):260–272. https://doi.org/10.1111/j.1471-4159.2008.05762.x

    CAS  Article  PubMed  Google Scholar 

  7. Malenka RC, Nicoll RA (1993) NMDA-receptor-dependent synaptic plasticity: multiple forms and mechanisms. Trends Neurosci 16(12):521–527. https://doi.org/10.1016/0166-2236(93)90197-t

    CAS  Article  PubMed  Google Scholar 

  8. Maltsev AV, Bal NV, Balaban PM (2019) LTP suppression by protein synthesis inhibitors is NO-dependent. Neuropharmacology. 146:276–288. https://doi.org/10.1016/j.neuropharm.2018.12.009

    CAS  Article  PubMed  Google Scholar 

  9. Morozov AV, Karpov VL (2018) Biological consequences of structural and functional proteasome diversity. Heliyon 4(10):e00894. Published 2018 Nov 2. https://doi.org/10.1016/j.heliyon.2018.e00894

    Article  PubMed  PubMed Central  Google Scholar 

  10. Morozov AV, Astakhova TM, Garbuz DG, Krasnov GS, Bobkova NV, Zatsepina OG, Karpov VL, Evgen'ev MB (2017) Interplay between recombinant Hsp70 and proteasomes: proteasome activity modulation and ubiquitin-independent cleavage of Hsp70. Cell Stress Chaperones 22(5):687–697. https://doi.org/10.1007/s12192-017-0792-y

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. Muchamuel T, Basler M, Aujay MA, Suzuki E, Kalim KW, Lauer C, Sylvain C, Ring ER, Shields J, Jiang J, Shwonek P, Parlati F, Demo SD, Bennett MK, Kirk CJ, Groettrup M (2009) A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. Nat Med 15(7):781–787. https://doi.org/10.1038/nm.1978

    CAS  Article  PubMed  Google Scholar 

  12. Orre M, Kamphuis W, Dooves S, Kooijman L, Chan ET, Kirk CJ, Dimayuga Smith V, Koot S, Mamber C, Jansen AH, Ovaa H, Hol EM (2013) Reactive glia show increased immunoproteasome activity in Alzheimer's disease. Brain 136(Pt 5):1415–1431. https://doi.org/10.1093/brain/awt083

    Article  PubMed  Google Scholar 

  13. Ramachandran KV, Margolis SS (2017) A mammalian nervous-system-specific plasma membrane proteasome complex that modulates neuronal function. Nat Struct Mol Biol 24(4):419–430. https://doi.org/10.1038/nsmb.3389

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. von Brzezinski L, Säring P, Landgraf P, Cammann C, Seifert U, Dieterich DC (2017) Low Neurotoxicity of ONX-0914 Supports the Idea of Specific Immunoproteasome Inhibition as a Side-Effect-Limiting, Therapeutic Strategy. Eur J Microbiol Immunol (Bp) 7(3):234–245. Published 2017 Sep 25. https://doi.org/10.1556/1886.2017.00025

    CAS  Article  Google Scholar 

Download references

Funding

The study was supported by the Russian Science Foundation grant 18–74-10095, electrophysiological experiments were supported by Russian Ministry of Science and Education (agreement #075–15–2020-801). The immunofluorescence was performed using equipment of the Core Centrum of Institute of Developmental Biology RAS. The work of AT, IV and LYu was supported by Government program of basic research in Koltzov Institute of Developmental Biology, Russian Academy of Sciences in 2020, No. 0108–2019–0002.

Author information

Affiliations

Authors

Contributions

All authors contributed to the study conception and design. The study was designed by Morozov Alexey, Bal Natalia and Karpov Vadim. Material preparation, data collection and analysis were performed by Maltsev Alexander, Funikov Sergei, Burov Alexander, Spasskaya Daria, Ignatyuk Vasilina, Astakhova Tatjana, Lyupina Yu., Tutyaeva Vera, Deikin Alexey, Bal Natalia, Karpov Vadim and Morozov Alexey. The first draft of the manuscript was written by Morozov Alexey and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Alexey Morozov.

Ethics declarations

Conflicts of Interest/Competing Interests

Authors declare no conflicts of interests.

Ethics Approval

All experiments were performed in accordance with the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Research Purposes 1986 86/609 / EEC and the institutional requirements for the care and use of laboratory animals (Institute of Higher Nervous Activity and Neurophysiology, RAS, Russia).

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Code Availability

Not applicable

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(DOCX 19 kb)

ESM 2

Suppl. Figure. Analysis of the anti-β5i antibodies. a. The antibodies were obtained after immunization of rabbits with the C-terminal murine β5i peptide (in red) conjugated with ovalbumin. After the third immunization animal sera were analyzed by immunoblotting with the 20S immunoproteasome (Enzo, USA) as the antigen (b). All animal sera were collected, and specific antibodies were obtained by affinity chromatography and tested as above (c). Immunoblotting of the purified recombinant β5i-subunit with the obtained antibodies (d). (PPTX 3593 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Maltsev, A., Funikov, S., Burov, A. et al. Immunoproteasome Inhibitor ONX-0914 Affects Long-Term Potentiation in Murine Hippocampus. J Neuroimmune Pharmacol (2021). https://doi.org/10.1007/s11481-020-09973-0

Download citation

Keywords

  • Proteasome
  • Immunoproteasome
  • Proteasome inhibitor
  • ONX-0914
  • Synaptic plasticity