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

Abstract

The ubiquitin-proteasome system (UPS) provides hydrolysis of most intracellular proteins in proteasomes. There are various forms of proteasomes differing, 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 (non-constitutive proteasomes), was shown. Here, we studied dynamic changes in the expression of catalytic proteasome subunit genes and protein content in the cerebral cortex of animals using a mouse model of AD (5xFAD transgenic mice). In samples from 5xFAD mice, at the age of 380 days, compared with samples from mice of 60 days of age, 4 and 6 times more gene transcripts of the immune subunits PSMB9 and PSMB8 were detected, as well as a significant increase in the number of immune β-subunits (2.8 times – β1i, 2.2 times – β2i) was observed. The results obtained indicate activation of the synthesis of immune subunits and assembly of non-constitutive proteasomes at the terminal stage of pathology development. At the same time, the results of electrophoresis in native conditions indicate the activation of both 20S and 26S proteasomes containing immune subunits in samples from 5xFAD mice, 380 days of age. The obtained data, in combination with available literature, indicate that the activation of non-constitutive proteasomes is a universal phenomenon characteristic of various animal models of AD, that may reflect both the development of neuroinflammation and adaptive processes in tissues.