Testing the ubiquitin-proteasome hypothesis of neurodegeneration in vivo
Testing the ubiquitin-proteasome hypothesis of neurodegeneration in vivo
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DOI：
10.1016/j.tins.2003.12.002
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发表时间：
2004-02-01
影响因子：
15.9
通讯作者：
Lucas, JJ
中科院分区：
文献类型：
--
作者：
Hernández, F;Díaz-Hernández, M;Lucas, JJ
大多数神经退行性疾病的一个共同的组织病理学标志是在受影响的神经元内存在异常的蛋白质包涵体。由于这些蛋白质聚集体是使用针对泛素-蛋白酶体系统（UPS）的组分的抗体检测的，因此已经表明这种用于调节蛋白质水解的机制的损伤是神经变性的根源。由于缺乏适当的工具，这一假设很难在体内证明。最近报道的转基因小鼠普遍表达的UPS报告蛋白应该最终有可能在体内测试的UPS在神经退行性变中的作用。
A common histopathological hallmark of most neurodegenerative diseases is the presence of aberrant proteinaceous inclusions inside affected neurons. Because these protein aggregates are detected using antibodies against components of the ubiquitin-proteasome system (UPS), impairment of this machinery for regulated proteolysis has been suggested to be at the root of neurodegeneration. This hypothesis has been difficult to prove in vivo owing to the lack of appropriate tools. The recent report of transgenic mice with ubiquitous expression of a UPS-reporter protein should finally make it possible to test in vivo the role of the UPS in neurodegeneration.