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.

摘要：泛素蛋白酶体系统（UPS）提供蛋白酶体中大多数细胞内蛋白质的水解作用。蛋白酶体有多种形式，其不同之处在于蛋白水解亚基的集合和激活剂的存在。阿尔茨海默病 (AD) 的特点是 UPS 功能状态紊乱。同时，某些形式的蛋白酶体，特别是含有免疫亚基的蛋白酶体（非组成型蛋白酶体）的表达增加。在这里，我们使用 AD 小鼠模型（5xFAD 转基因小鼠）研究了动物大脑皮质中催化蛋白酶体亚基基因和相应蛋白质表达的动态变化。PSMB9和PSMB8的转录本增加了 4 倍和 6 倍与来自 5xFAD 小鼠的样本相比，在 380 天龄的 5xFAD 小鼠样本中检测到了编码免疫蛋白酶体亚基的基因，并且免疫β亚基的含量显着增加（β1i 增加了 2.8 倍；β2i 增加了 2.2 倍）。 60天龄的小鼠。此外，通过天然条件下的电泳，在 380 天大的 5xFAD 小鼠样本中发现了含有免疫亚基的 20S 和 26S 蛋白酶体的激活。这表明在病理发展的末期，免疫亚基的合成和非组成型蛋白酶体的组装被激活。获得的数据结合现有文献表明，非组成型蛋白酶体的激活是各种 AD 动物模型的普遍现象特征，