In the nervous system, proteasomes are important for proteolysis and cellular homeostasis of neurons and glial cells and for brain health. Proteasome function declines with age in many tissues, including the nervous system, and this decline affects many of the nervous system processes important to brain health and may be related to age‐related cognitive decline. Therefore, we analyzed the factors that contribute to this decline in function using the brain of mice from different months of life. Peptidase activity of proteasomes in crude extracts decreased with aging, while ubiquitinated proteins increased with aging. Additionally, there was a tendency for the number of subunits that form proteasomes to decrease slightly with age. On the other hand, ump1, which is required for proteasome formation, accumulated with age. Therefore, analysis of proteasome dynamics in each month revealed that proteasome formation decreased with aging. This study suggests that with aging, not only 20S proteasome function but also 26 proteasome function decreases, the decline in proteasome function is due to the lack of proteasome formation, the PA28‐20S‐PA700 complex, which is involved in immunity, increases in the brain, and one factor in this lack of proteasome formation is that the proteins called UMP1.

中文翻译：

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与衰老相关的大脑蛋白酶体动力学变化

在神经系统中，蛋白酶体对于神经元和神经胶质细胞的蛋白水解和细胞稳态以及大脑健康非常重要。许多组织（包括神经系统）中的蛋白酶体功能随着年龄的增长而下降，这种下降会影响许多对大脑健康很重要的神经系统过程，并可能与年龄相关的认知能力下降有关。因此，我们利用不同月份小鼠的大脑分析了导致这种功能下降的因素。粗提物中蛋白酶体的肽酶活性随着年龄的增长而降低，而泛素化蛋白的活性则随着年龄的增长而增加。此外，随着年龄的增长，形成蛋白酶体的亚基数量有轻微减少的趋势。另一方面，蛋白酶体形成所需的ump1随着年龄的增长而积累。因此，每个月的蛋白酶体动态分析表明，蛋白酶体的形成随着年龄的增长而减少。本研究提示，随着衰老，不仅20S蛋白酶体功能下降，26蛋白酶体功能也下降，蛋白酶体功能下降是由于蛋白酶体形成不足，参与免疫的PA28-20S-PA700复合物增加，大脑中缺乏蛋白酶体形成的因素之一是名为 UMP1 的蛋白质。