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Pregnane X Receptor and P-glycoprotein: a connexion for Alzheimer’s disease management

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Abstract

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 (A\(\upbeta \)) 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 A\(\upbeta \) from brain alongside and inhibits the apical to basolateral movement of A\(\upbeta \) 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.

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Acknowledgments

This work was supported by the Department of Biotechnology (DBT), India.

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  1. Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Sector 67, Mohali, 160062, Punjab, India

    Sumit Jain, Vijay Rathod, Rameshwar Prajapati, Prajwal P. Nandekar & Abhay T. Sangamwar

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  1. Sumit Jain
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  2. Vijay Rathod
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Correspondence to Abhay T. Sangamwar.

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Sumit Jain, Vijay Rathod and Rameshwar Prajapati have contributed equally to this study.

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Jain, S., Rathod, V., Prajapati, R. et al. Pregnane X Receptor and P-glycoprotein: a connexion for Alzheimer’s disease management. Mol Divers 18, 895–909 (2014). https://doi.org/10.1007/s11030-014-9550-6

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