Chadwick Wayne, Brenneman Randall, Martin Bronwen, Maudsley Stuart
Receptor Pharmacology Unit, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USA.
Int J Alzheimers Dis. 2010 Dec 2;2010:604792. doi: 10.4061/2010/604792.
Various animal models of Alzheimer's disease (AD) have been created to assist our appreciation of AD pathophysiology, as well as aid development of novel therapeutic strategies. Despite the discovery of mutated proteins that predict the development of AD, there are likely to be many other proteins also involved in this disorder. Complex physiological processes are mediated by coherent interactions of clusters of functionally related proteins. Synaptic dysfunction is one of the hallmarks of AD. Synaptic proteins are organized into multiprotein complexes in high-density membrane structures, known as lipid rafts. These microdomains enable coherent clustering of synergistic signaling proteins. We have used mass analytical techniques and multiple bioinformatic approaches to better appreciate the intricate interactions of these multifunctional proteins in the 3xTgAD murine model of AD. Our results show that there are significant alterations in numerous receptor/cell signaling proteins in cortical lipid rafts isolated from 3xTgAD mice.
人们已经创建了各种阿尔茨海默病（AD）动物模型，以帮助我们理解AD的病理生理学，并辅助新型治疗策略的开发。尽管发现了可预测AD发病的突变蛋白，但可能还有许多其他蛋白质也参与了这种疾病。复杂的生理过程是由功能相关蛋白质簇的协同相互作用介导的。突触功能障碍是AD的标志性特征之一。突触蛋白在称为脂筏的高密度膜结构中组织成多蛋白复合物。这些微结构域能够使协同信号蛋白进行连贯聚集。我们使用了质谱分析技术和多种生物信息学方法，以更好地理解这些多功能蛋白在AD的3xTgAD小鼠模型中的复杂相互作用。我们的结果表明，从3xTgAD小鼠分离的皮质脂筏中，众多受体/细胞信号蛋白存在显著改变。
