title: Pregnane X Receptor and P-glycoprotein: a connexion for Alzheimer's disease management.
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 (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.
authors.affiliation: Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Sector 67, Mohali, 160062, Punjab, India.
authors.forename: Sumit
authors.initials: S
authors.lastname: Jain
authors.forename: Vijay
authors.initials: V
authors.lastname: Rathod
authors.forename: Rameshwar
authors.initials: R
authors.lastname: Prajapati
authors.forename: Prajwal P
authors.initials: PP
authors.lastname: Nandekar
authors.forename: Abhay T
authors.initials: AT
authors.lastname: Sangamwar
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D019468:Disease Management; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D008958:Models, Molecular; D058990:Molecular Targeted Therapy; D000077297:Pregnane X Receptor; D011485:Protein Binding; D011487:Protein Conformation; D011987:Receptors, Steroid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid