van Tijn Paula, Hol Elly M, van Leeuwen Fred W, Fischer David F
Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
Prog Neurobiol. 2008 Jun;85(2):176-93. doi: 10.1016/j.pneurobio.2008.03.001. Epub 2008 Mar 18.
The ubiquitin-proteasome system (UPS) is the main intracellular pathway for regulated protein turnover. This system is of vital importance for maintaining cellular homeostasis and is essential for neuronal functioning. It is therefore not surprising that impairment of this system is implicated in the pathogenesis of a variety of diseases, including neurological disorders, which are pathologically characterized by the presence of ubiquitin-positive protein aggregates. A direct correlation between intact neuronal functioning and the UPS is exemplified by a range of transgenic mouse models wherein mutations in components of the UPS lead to a neurodegenerative or neurological phenotype. These models have been proven useful in determining the role of the UPS in the nervous system in health and disease. Furthermore, recently developed in vivo models harboring reporter systems to measure UPS activity could also substantially contribute to understanding the effect of neurodegeneration on UPS function. The role of the UPS in neurodegeneration in vivo is reviewed by discussing the currently available murine models showing a neurological phenotype induced by genetic manipulation of the UPS.
泛素-蛋白酶体系统（UPS）是细胞内调节蛋白质周转的主要途径。该系统对于维持细胞内稳态至关重要，并且对神经元功能起着不可或缺的作用。因此，该系统的损伤与多种疾病的发病机制有关也就不足为奇了，这些疾病包括神经障碍，其病理特征为存在泛素阳性蛋白聚集体。完整的神经元功能与UPS之间的直接关联在一系列转基因小鼠模型中得到了例证，其中UPS组分的突变会导致神经退行性或神经学表型。这些模型已被证明在确定UPS在健康和疾病状态下神经系统中的作用方面很有用。此外，最近开发的带有报告系统以测量UPS活性的体内模型也可能极大地有助于理解神经退行性变对UPS功能的影响。通过讨论目前可用的显示由UPS基因操作诱导的神经学表型的小鼠模型，对UPS在体内神经退行性变中的作用进行了综述。
