文章基本信息

标题：Increased expression of p62/SQSTM1 in prion diseases and its association with pathogenic prion protein
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作者：Takujiro Homma ; Daisuke Ishibashi ; Takehiro Nakagaki 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2014
卷号：4
DOI：10.1038/srep04504
出版社：Springer Nature
摘要：Prion diseases are neurodegenerative disorders characterized by the aggregation of abnormally folded prion protein (PrP^Sc). In this study, we focused on the mechanism of clearance of PrP^Sc, which remains unclear. p62 is a cytosolic protein known to mediate both the formation and degradation of aggregates of abnormal proteins. The levels of p62 protein increased in prion-infected brains and persistently infected cell cultures. Upon proteasome inhibition, p62 co-localized with PrP^Sc, forming a large aggregate in the perinuclear region, hereafter referred to as PrP^Sc-aggresome. These aggregates were surrounded with autophagosome marker LC3 and lysosomes in prion-infected cells. Moreover, transient expression of the phosphomimic form of p62, which has enhanced ubiquitin-binding activity, reduced the amount of PrP^Sc in prion-infected cells, indicating that the activation of p62 could accelerate the clearance of PrP^Sc. Our findings would thus suggest that p62 could be a target for the therapeutic control of prion diseases.