Shin Baehyun, Oh Hyejin, Park Sang Min, Han Hye-Eun, Ye Michael, Song Woo Keun, Park Woo Jin
School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea; Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Bio Imaging and Cell Dynamics Research Center, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea; Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
PLoS One. 2014 Jun 10;9(6):e98650. doi: 10.1371/journal.pone.0098650. eCollection 2014.
Nuclear inclusion a (NIa) of turnip mosaic virus is a cytosolic protease that cleaves amyloid β (Aβ) when heterologously overexpressed. Lentivirus-mediated expression of NIa in the brains of APP(sw)/PS1 mice significantly reduces cerebral Aβ levels and plaque depositions, and improves behavioral deficits. Here, the effects of NIa and neprilysin (NEP), a well-known Aβ-cleaving protease, on oligomeric Aβ-induced cell death were evaluated. NIa cleaved monomeric and oligomeric Aβ at a similar rate, whereas NEP only cleaved monomeric Aβ. Oligomeric Aβ-induced cytotoxicity and mitochondrial dysfunction were significantly ameliorated by NIa, but not by NEP. Endocytosed fluorescently-labeled Aβ localized to mitochondria, and this was significantly reduced by NIa, but not by NEP. These data suggest that NIa may exerts its protective roles by degrading Aβ and thus preventing mitochondrial deposition of Aβ.
芜菁花叶病毒的核内含体a（NIa）是一种胞质蛋白酶，在异源过表达时可切割淀粉样β蛋白（Aβ）。慢病毒介导的NIa在APP(sw)/PS1小鼠大脑中的表达显著降低了脑内Aβ水平和斑块沉积，并改善了行为缺陷。在此，评估了NIa和一种著名的Aβ切割蛋白酶中性内肽酶（NEP）对寡聚Aβ诱导的细胞死亡的影响。NIa以相似的速率切割单体和寡聚Aβ，而NEP仅切割单体Aβ。NIa可显著改善寡聚Aβ诱导的细胞毒性和线粒体功能障碍，而NEP则不能。内吞的荧光标记Aβ定位于线粒体，NIa可显著减少这种情况，而NEP则不能。这些数据表明，NIa可能通过降解Aβ从而防止Aβ在线粒体沉积发挥其保护作用。
