Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Sant Joan d'Alacant, E-03550, Spain.
Neurobiol Dis. 2010 Mar;37(3):682-91. doi: 10.1016/j.nbd.2009.12.006. Epub 2009 Dec 16.
Reelin is a glycoprotein that modulates synaptic function and plasticity in the mature brain, thereby favouring memory formation. We recently reported altered cerebral Reelin expression in Alzheimer's disease (AD). Here we demonstrate pronounced Reelin changes at protein and mRNA levels in the frontal cortex in adult Down's syndrome (DS), where the extra copy of chromosome 21 leads to overexpression of beta-amyloid. In cortical extracts of fetal DS samples we detected increased levels of the full-length Reelin and the 310-kDa fragment. Overexpression of mutant human amyloid precursor protein also led to an increase in levels of Reelin fragments in Tg2576 transgenic mice for human beta-amyloid. Finally, in vitro Abeta42 treatment of SH-SY5Y neuroblastoma cells led to increased Reelin levels. An altered pattern of Reelin glycosylation was detected in extracts from the frontal cortex of AD patients and in Abeta42-treated SH-SY5Y cells, supporting the notion that beta-amyloid triggers altered Reelin processing. These results provide evidence that Reelin expression and processing is altered in several amyloid conditions.
Reelin 是一种糖蛋白，可调节成熟大脑中的突触功能和可塑性，从而有利于记忆形成。我们最近报道了阿尔茨海默病（AD）患者大脑 Reelin 表达改变。在这里，我们在成年唐氏综合征（DS）患者的额叶皮层中证明了 Reelin 在蛋白质和 mRNA 水平上的明显变化，其中 21 号染色体的额外拷贝导致β-淀粉样蛋白过度表达。在胎儿 DS 样本的皮质提取物中，我们检测到全长 Reelin 和 310 kDa 片段的水平增加。突变型人淀粉样前体蛋白的过表达也导致 Tg2576 转基因小鼠中用于人β-淀粉样蛋白的 Reelin 片段水平增加。最后，体外 Abeta42 处理 SH-SY5Y 神经母细胞瘤细胞导致 Reelin 水平增加。在 AD 患者的额叶皮层提取物和 Abeta42 处理的 SH-SY5Y 细胞中检测到 Reelin 糖基化模式改变，支持β-淀粉样蛋白引发改变的 Reelin 处理的观点。这些结果提供了证据，表明几种淀粉样条件下 Reelin 的表达和加工发生改变。
