Program on Cell and Neurobiology of Energy Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Neuroscience Group, Instituto de Investigacion Hospital 12 de Octubre (i+12), Madrid, Spain Center for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
J Alzheimers Dis. 2014;39(4):711-7. doi: 10.3233/JAD-131604.
Megalin has been suggested to be involved in Alzheimer's disease (AD), mediating blood-brain barrier (BBB) transport of multiple ligands, including amyloid-β peptide (Aβ), but also neuroprotective factors. Because no transgenic model is currently available to study this concept, we have obtained transgenic mice blocking megalin expression at the BBB. These endothelial megalin deficient (EMD) mice developed increased anxiety behavior and impaired learning ability and recognition memory, similar to symptoms described in AD. Degenerating neurons were also observed in the cerebral cortex of EMD mice. In view of our findings we suggest that, in mice, megalin deficiency at the BBB leads to neurodegeneration.
巨球蛋白受体（megalin）被认为与阿尔茨海默病（AD）有关，可介导包括淀粉样β肽（Aβ）在内的多种配体通过血脑屏障（BBB）的转运，同时也具有神经保护作用。由于目前尚无转基因模型可用于研究这一概念，我们获得了在血脑屏障阻断巨球蛋白受体表达的转基因小鼠。这些内皮细胞巨球蛋白受体缺失（EMD）小鼠表现出焦虑行为增加、学习能力和识别记忆受损，与 AD 描述的症状相似。在 EMD 小鼠的大脑皮层中也观察到神经元退化。鉴于我们的发现，我们认为在小鼠中，血脑屏障的巨球蛋白受体缺失会导致神经退行性变。
