Institut für Biochemie, Charité-Universitätsmedizin-Berlin, Berlin, Germany.
PLoS One. 2013 May 7;8(5):e64042. doi: 10.1371/journal.pone.0064042. Print 2013.
Proteostasis is critical for the maintenance of life. In neuronal cells an imbalance between protein synthesis and degradation is thought to be involved in the pathogenesis of neurodegenerative diseases during aging. Partly, this seems to be due to a decrease in the activity of the ubiquitin-proteasome system, wherein the 20S/26S proteasome complexes catalyse the proteolytic step. We have characterised 20S and 26S proteasomes from cerebrum, cerebellum and hippocampus of 3 weeks old (young) and 24 month old (aged) rats. Our data reveal that the absolute amount of the proteasome is not dfferent between both age groups. Within the majority of standard proteasomes in brain the minute amounts of immuno-subunits are slightly increased in aged rat brain. While this goes along with a decrease in the activities of 20S and 26S proteasomes to hydrolyse synthetic fluorogenic tripeptide substrates from young to aged rats, the capacity of 26S proteasomes for degradation of poly-Ub-model substrates and its activation by poly-Ub-substrates is not impaired or even slightly increased in brain of aged rats. We conclude that these alterations in proteasome properties are important for maintaining proteostasis in the brain during an uncomplicated aging process.
蛋白质稳态对于生命的维持至关重要。在神经元细胞中，蛋白质合成和降解之间的失衡被认为与衰老过程中神经退行性疾病的发病机制有关。部分原因似乎是由于泛素-蛋白酶体系统的活性下降，其中 20S/26S 蛋白酶体复合物催化蛋白水解步骤。我们已经从 3 周龄（年轻）和 24 月龄（年老）大鼠的大脑、小脑和海马体中鉴定了 20S 和 26S 蛋白酶体。我们的数据表明，两组年龄之间的蛋白酶体绝对数量没有差异。在大脑中的大多数标准蛋白酶体中，免疫亚基的微量含量在老年大鼠大脑中略有增加。虽然这与从年轻到年老大鼠的 20S 和 26S 蛋白酶体水解合成荧光三肽底物的活性下降有关，但 26S 蛋白酶体降解多聚 Ub 模型底物的能力及其被多聚 Ub 底物激活的能力在年老大鼠的大脑中没有受损，甚至略有增加。我们得出结论，这些蛋白酶体特性的改变对于在简单的衰老过程中维持大脑中的蛋白质稳态是重要的。
