2022  1,200
2021  1,540
2020  1,374
2019  1,023
2018  0,932
2017  0,977
2016  0,799
2015  0,662
2014  0,740
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 57(2023) N 5 p. 885-896; DOI 10.1134/S0026893323050138 Full Text

A.V. Morozov1*, A.V. Burov1, S.Yu. Funikov1, E.V. Teterina2, T.M. Astakhova3, P.A. Erokhov3, A.A. Ustyugov2, V.L. Karpov1

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

1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
2Institute of Physiologically Active Substances, Russian Academy of Sciences, Chernogolovka, 142432 Russia
3Koltsov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, 119334 Russia

Received - 2023-03-04; Revised - 2023-03-20; Accepted - 2023-03-21

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.

Alzheimer's disease, proteasomes, nonconstitutive proteasomes