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Changes in the Activities and Contents of Individual Forms of Proteasomes in Samples of the Cerebral Cortex during Pathology Development in 5xFAD Mice

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Abstract—The ubiquitin-proteasome system (UPS) provides hydrolysis of most intracellular proteins in proteasomes. There are various forms of proteasomes that differ, among other things, in the set of proteolytic subunits and the presence of activators. Alzheimer’s disease (AD) is characterized by disturbances in the functional state of the UPS. At the same time, an increase in the expression of certain forms of proteasomes, in particular, proteasomes containing immune subunits (nonconstitutive proteasomes), has been shown. Here, we studied dynamic changes in the expression of catalytic proteasome subunit genes and corresponding proteins in the cerebral cortex of animals using a mouse model of AD (5xFAD transgenic mice). Increases by 4 and 6 folds in transcripts of the PSMB9 and PSMB8 genes encoding immune proteasome subunits were detected, as well as a significant increase in the content of immune β-subunits (by 2.8 folds, β1i; 2.2 folds, β2i) in samples from 5xFAD mice at the age of 380 days, compared with samples from mice at 60 days of age. Moreover, the activation of both 20S and 26S proteasomes containing immune subunits were revealed in samples from 380 days old 5xFAD mice by electrophoresis in native conditions. This indicates activated synthesis of the immune subunits and assembly of nonconstitutive proteasomes at the terminal stage of pathology development. The obtained data, in combination with the available literature, indicate that the activation of nonconstitutive proteasomes is a universal phenomenon characteristic of various animal models of AD, which may reflect both the development of neuroinflammation and adaptive processes in tissues induced by the accumulation of toxic protein aggegates.

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Funding

The work received financial support from the Russian Science Foundation (grant no. 18-74-10095).

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Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russia

    A. V. Morozov, A. V. Burov, S. Yu. Funikov & V. L. Karpov

  2. Institute of Physiologically Active Substances, Russian Academy of Sciences, 142432, Chernogolovka, Moscow oblast, Russia

    E. V. Teterina & A. A. Ustyugov

  3. Koltsov Institute of Developmental Biology, Russian Academy of Sciences, 119334, Moscow, Russia

    T. M. Astakhova & P. A. Erokhov

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  1. A. V. Morozov
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  2. A. V. Burov
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  3. S. Yu. Funikov
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  4. E. V. Teterina
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  5. T. M. Astakhova
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Correspondence to A. V. Morozov.

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Statement on the welfare of animals. Work with animals was carried out in accordance with the “Rules of laboratory practice in the Russian Federation” dated April 1, 2016 No. 199n.

Conflict of interest. The authors declare that they have no conflicts of interest.

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Morozov, A.V., Burov, A.V., Funikov, S.Y. et al. Changes in the Activities and Contents of Individual Forms of Proteasomes in Samples of the Cerebral Cortex during Pathology Development in 5xFAD Mice. Mol Biol 57, 885–896 (2023). https://doi.org/10.1134/S0026893323050138

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