Yang Hui, Hu Hong-Yu
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
FEBS J. 2016 Oct;283(20):3705-3717. doi: 10.1111/febs.13722. Epub 2016 May 6.
Protein misfolding and aggregation are a hallmark of several neurodegenerative diseases (NDs). However, how protein aggregation leads to cytotoxicity and neurodegeneration is still controversial. Emerging evidence demonstrates that sequestration of cellular-interacting partners by protein aggregates contributes to the pathogenesis of these diseases. Here, we review current research on sequestration of cellular proteins by protein aggregates and its relation to proteinopathies. Based on different interaction modes, we classify these protein sequestrations into four types: protein coaggregation, domain/motif-mediated sequestration, RNA-assisted sequestration, and sequestration of molecular chaperones. Thus, the cellular essential proteins and/or RNA hijacked by protein aggregates may lose their biological functions, consequently resulting in cytotoxicity and neurodegeneration. We have proposed a hijacking model recapitulating the sequestration process and the loss-of-function pathology of ND.
蛋白质错误折叠和聚集是几种神经退行性疾病（NDs）的标志。然而，蛋白质聚集如何导致细胞毒性和神经退行性变仍存在争议。新出现的证据表明，蛋白质聚集体对细胞相互作用伙伴的隔离作用促成了这些疾病的发病机制。在这里，我们综述了目前关于蛋白质聚集体对细胞蛋白质的隔离作用及其与蛋白质病关系的研究。基于不同的相互作用模式，我们将这些蛋白质隔离分为四种类型：蛋白质共聚集、结构域/基序介导的隔离、RNA辅助的隔离以及分子伴侣的隔离。因此，被蛋白质聚集体劫持的细胞必需蛋白质和/或RNA可能会丧失其生物学功能，从而导致细胞毒性和神经退行性变。我们提出了一个劫持模型，概括了神经退行性疾病的隔离过程和功能丧失病理学。
