Jain Sumit, Rathod Vijay, Prajapati Rameshwar, Nandekar Prajwal P, Sangamwar Abhay T
Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Sector 67, Mohali, 160062, Punjab, India.
Mol Divers. 2014 Nov;18(4):895-909. doi: 10.1007/s11030-014-9550-6. Epub 2014 Sep 12.
The translational failure between preclinical animal models and clinical outcome has alarmed us to search for a new strategy in the treatment of Alzheimer's disease (AD). Interlink between Pregnane X Receptor (PXR) and P-glycoprotein (Pgp) at the blood brain barrier (BBB) has raised hope toward a new disease modifying therapy in AD. Pgp is a major efflux transporter for beta amyloid (Aβ) at human BBB. A literature survey reveals diminished expression of Pgp transporter at the BBB in AD patients. Pregnane X Receptor is a major transcriptional regulator of Pgp. Restoration of Pgp at the BBB enhances the elimination of the Aβ from brain alongside and inhibits the apical to basolateral movement of Aβ from the circulatory blood. This review concentrates on in vitro, in vivo, and in silico advancements on the study of the PXR in context to Pgp and discusses the substrate and inhibitor specificity between PXR and Pgp.
临床前动物模型与临床结果之间的转化失败促使我们寻找治疗阿尔茨海默病（AD）的新策略。孕烷X受体（PXR）与血脑屏障（BBB）处的P-糖蛋白（Pgp）之间的相互联系为AD的新型疾病修饰疗法带来了希望。Pgp是人类血脑屏障处β淀粉样蛋白（Aβ）的主要外排转运蛋白。文献调查显示，AD患者血脑屏障处Pgp转运蛋白的表达降低。孕烷X受体是Pgp的主要转录调节因子。血脑屏障处Pgp的恢复可增强Aβ从大脑中的清除，并抑制Aβ从循环血液中从顶端向基底外侧的移动。本综述集中于PXR与Pgp相关研究在体外、体内和计算机模拟方面的进展，并讨论PXR与Pgp之间的底物和抑制剂特异性。
