Valera Adriana G, Díaz-Hernández Miguel, Hernández Félix, Lucas José J
Centro de Biologia Molecular Severo Ochoa, CSIC/UAM, Campus UAM de Cantoblanco, Madrid, Spain.
Brain Res Bull. 2007 Apr 30;72(2-3):121-3. doi: 10.1016/j.brainresbull.2006.10.030. Epub 2006 Nov 20.
An impairment of the ubiquitin-proteasome system (UPS) has been postulated in Huntington's disease (HD) and in other CAG-triplet repeat disorders. This hypothesis arises from the observation that polyglutamine (polyQ)-containing inclusion bodies that are characteristic of these diseases also contain components of the UPS. However, since that initial discovery, the UPS impairment hypothesis has remained controversial. Recent in vitro enzymatic studies revealed the inability of eukaryotic proteasomes to digest expanded polyQ, thus suggesting that occasional failure of polyQ to exit the proteasome may interfere with its proteolytic function. However, it has also recently been found that in vitro assembled aggregates made of synthetic polyQ fail to inhibit proteasome activity. Here we propose future experiments that may help to ellucidate whether a direct interaction between proteasomes and polyQ stretches or aggregates can result in inhibition of proteasome activity.
泛素-蛋白酶体系统（UPS）功能受损已被推测与亨廷顿舞蹈病（HD）及其他CAG三核苷酸重复疾病有关。这一假设源于如下观察结果：这些疾病所特有的含多聚谷氨酰胺（polyQ）的包涵体也包含UPS的成分。然而，自最初发现以来，UPS功能受损假说一直存在争议。最近的体外酶学研究表明，真核生物蛋白酶体无法消化扩增的polyQ，因此提示polyQ偶尔无法从蛋白酶体中排出可能会干扰其蛋白水解功能。然而，最近还发现，由合成polyQ体外组装而成的聚集体无法抑制蛋白酶体活性。在此，我们提出了一些未来的实验，这些实验可能有助于阐明蛋白酶体与polyQ片段或聚集体之间的直接相互作用是否会导致蛋白酶体活性受到抑制。
