Cheng Zhi, Shang Yingchun, Gao Shan, Zhang Tao
a College of Life Sciences and Key Laboratory of Bioactive Materials Ministry of Education , Nankai University , Tianjin , PR China.
J Neurogenet. 2017 Dec;31(4):337-343. doi: 10.1080/01677063.2017.1395425. Epub 2017 Nov 3.
We recently reported that presenilin-1 (PS1) induced an increase of U1 snRNA expression accompanied with the change of amyloid precursor protein expression, β-amyloid level and cell death. In the present study, our data showed that both overexpression and knockdown of U1 snRNA could cause the loss in the function of U1 snRNA and resulted in PCPA as well as the same downstream phenomena including the expression changes of genes specific to AD, tau hyperphosphorylation on the site of Thr212, the decrease of acetylated α-tubulin, the reduction of cell viability and upregulation of RIPK1, RIPK3 and caspase8. These findings not only helped researchers better understand the functions of U1 snRNA, but also paved the way to reveal the mechanisms of AD from a different point of view and may find a new therapeutic target for the disease.
我们最近报道，早老素-1（PS1）诱导U1小核RNA（U1 snRNA）表达增加，同时伴有淀粉样前体蛋白表达、β-淀粉样蛋白水平和细胞死亡的变化。在本研究中，我们的数据表明，U1 snRNA的过表达和敲低均可导致U1 snRNA功能丧失，并导致早老素相关蛋白异常加工（PCPA）以及相同的下游现象，包括阿尔茨海默病（AD）特异性基因的表达变化、苏氨酸212位点的tau蛋白过度磷酸化、乙酰化α-微管蛋白减少、细胞活力降低以及受体相互作用蛋白激酶1（RIPK1）、受体相互作用蛋白激酶3（RIPK3）和半胱天冬酶8（caspase8）上调。这些发现不仅有助于研究人员更好地理解U1 snRNA的功能，还为从不同角度揭示AD的发病机制铺平了道路，并可能为该疾病找到新的治疗靶点。
