Zeng B-Y, Medhurst A D, Jackson M, Rose S, Jenner P
Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London, UK.
Mech Ageing Dev. 2005 Jun-Jul;126(6-7):760-6. doi: 10.1016/j.mad.2005.01.008. Epub 2005 Mar 5.
Age-related increase in protein oxidation in brain coupled to an impairment of proteasomal activity may underline neuronal loss but differences in susceptibility between species and brain regions remain unexplained. We now investigate differences in proteasomal activity, measured as chymotrypsin-, trypsin- and peptidylglutamyl-like hydrolysing activities between brain regions in rats, mice and common marmosets. In aged rats and mice, proteasomal activity was decreased in the cortex, striatum, cerebellum, globus pallidus and substantia nigra overall when compared to young animals. However, in the aged brain only chymotrypsin-like activity was decreased in the cortex and the globus pallidus while only trypsin-like activity was reduced in the cerebellum. In contrast, in the striatum, both chymotrypsin-like and trypsin-like activities were reduced and in the substantia nigra, all the three catalytic activities of proteasome were significantly impaired. Chymotrypsin-like and trypsin-like activities were significantly higher in all the brain regions of marmosets compared to those of mice and rats. Peptidylglutamyl-like activity was only significantly higher in the cerebellum and striatum of marmoset compared to rodents. The data suggest that there is higher proteasome activity in common marmoset brain compared to rat and mouse and that the basal ganglia are more prone to an age-related decrease in proteasomal activity. This may explain the involvement of altered ubiquitin-proteasome system activity in Parkinson's disease and the relationship to ageing.
大脑中与年龄相关的蛋白质氧化增加以及蛋白酶体活性受损可能是神经元丢失的潜在原因，但物种和脑区之间易感性的差异仍未得到解释。我们现在研究大鼠、小鼠和普通狨猴脑区之间蛋白酶体活性的差异，以胰凝乳蛋白酶、胰蛋白酶和肽基谷氨酰基样水解活性来衡量。与年轻动物相比，老年大鼠和小鼠的大脑皮质、纹状体、小脑、苍白球和黑质中的蛋白酶体活性总体上有所下降。然而，在老年大脑中，仅大脑皮质和苍白球中的胰凝乳蛋白酶样活性下降，而仅小脑中的胰蛋白酶样活性降低。相比之下，在纹状体中，胰凝乳蛋白酶样和胰蛋白酶样活性均降低，在黑质中，蛋白酶体的所有三种催化活性均显著受损。与小鼠和大鼠相比，狨猴所有脑区的胰凝乳蛋白酶样和胰蛋白酶样活性均显著更高。与啮齿动物相比，肽基谷氨酰基样活性仅在狨猴的小脑和纹状体中显著更高。数据表明，与大鼠和小鼠相比，普通狨猴大脑中的蛋白酶体活性更高，并且基底神经节更容易出现与年龄相关的蛋白酶体活性下降。这可能解释了泛素 - 蛋白酶体系统活性改变在帕金森病中的作用以及与衰老的关系。
