Vigouroux Sophie, Briand Marièle, Briand Yves
Laboratoire de Biochimie Appliquée, Associé INRA, Université Blaise Pascal, 63 174 Aubière, France.
Mol Neurobiol. 2004 Oct;30(2):201-21. doi: 10.1385/MN:30:2:201.
During aging, the production of free radicals increases. This can result in damage to protein, the accumulation of which is characteristic of the aging process. This questions the efficacy of proteolytic systems. Among these systems, the proteasome and the adenosine triphosphate-ubiquitin-dependent pathway have been shown to play an important role in the elimination of abnormal proteins. There are two major steps in the ubiquitin-proteasome pathway: the conjugation of a polyubiquitin degradation signal to the substrate and the subsequent degradation of the tagged protein by the 26S proteasome. The 26S proteasome is build-up from the 20S proteasome, which is a cylinder-shaped multimeric complex, and two additional 19S complexes. The 20S proteasome can also bind to 11S regulator and is then implicated in antigen presentation. These regulators confer a high adaptability on proteasome. With advancing age, predisposition to neurodegenerative diseases increases. These diseases are also characterized by protein aggregation. Several findings such as the presence of ubiquinated proteins, usually broken down by proteasomes, and genetic anomalies involving the ubiquitin-proteasome system (parkin, UCH-L1) suggest a link between the ubiquitin-proteasome pathway and the genesis of these diseases.
在衰老过程中，自由基的产生会增加。这可能导致蛋白质受损，而蛋白质的积累是衰老过程的特征。这对蛋白水解系统的功效提出了质疑。在这些系统中，蛋白酶体和三磷酸腺苷-泛素依赖性途径已被证明在清除异常蛋白质方面发挥重要作用。泛素-蛋白酶体途径有两个主要步骤：将多聚泛素降解信号与底物结合，以及随后由26S蛋白酶体降解标记的蛋白质。26S蛋白酶体由20S蛋白酶体（一种圆柱形多聚体复合物）和另外两个19S复合物组成。20S蛋白酶体也可以与11S调节因子结合，进而参与抗原呈递。这些调节因子赋予蛋白酶体高度的适应性。随着年龄的增长，患神经退行性疾病的倾向会增加。这些疾病也以蛋白质聚集为特征。一些发现，如通常由蛋白酶体分解的泛素化蛋白质的存在，以及涉及泛素-蛋白酶体系统（帕金蛋白、泛素羧基末端水解酶L1）的基因异常，表明泛素-蛋白酶体途径与这些疾病的发生之间存在联系。
