Aggresomes——错误折叠蛋白的一种普遍细胞反应

Aggresomes-a general cellular response to misfolded protein

通常,细胞中的错误折叠蛋白质会被蛋白酶体降解。但是在一定的病理和生理条件下,一些错误折叠蛋白质几乎不被降解,反而可以形成蛋白质聚集体。研究表明,许多疾病,如神经退行性疾病的发病机理与错误折叠蛋白质在细胞内的聚集体沉积有关。这些蛋白质聚集体可以通过微管上动力蛋白依赖的逆行性运输形式传送、聚集,最终形成aggresomes。最新的报道还指出,蛋白质聚集体能直接损伤泛素—蛋白酶体系统的功能,从而引起细胞的调控紊乱和细胞死亡。

Generally, misfolded proteins are degraded by proteasomes. But under some pathological and physiological conditions, hardly are these misfolded proteins degraded while they can be formed accumulation of protein aggregates. Some studies suggested that the pathogenesis of many diseases such as neurodegenerative disease are related to the accumulation of misfolded protein aggregates in cell. These aggregates are specifically carried together by dynein-dependent retrograde transport on microtubles, ultimately forming aggresomes. The latest reports point out that protein aggregation directly impair the function of the ubiquityin-proteasome system, then leading to cellular disregulation and cell death.