ATP-binding cassette sub-family B member 1 (P-glycoprotein) (ABCB1)

P-glycoprotein (P-gp), encoded by the ABCB1 gene, is a crucial ATP-binding cassette transporter located on the luminal surface of brain capillary endothelial cells, where it constitutes a primary element of the blood-brain barrier (BBB) [UniProt: P08183]. Its main biological role is the ATP-dependent efflux of diverse lipophilic compounds, including xenobiotics and metabolic waste, from the brain into the blood to maintain CNS homeostasis [StatPearls: P-glycoprotein]. Verapamil is a well-known substrate and competitive inhibitor of P-gp; consequently, [11C]verapamil positron emission tomography (PET) is frequently used as a gold-standard biomarker to quantify P-gp function at the human BBB in vivo [PMID: 15901798]. In disease states, P-gp overexpression is a hallmark of multidrug resistance in various cancers and is linked to pharmacoresistance in epilepsy by preventing antiepileptic drugs from reaching their targets [NCBI: ABCB1]. Conversely, reduced P-gp activity at the BBB is associated with neurodegenerative conditions like Alzheimer's disease, potentially hindering the clearance of amyloid-beta peptides [PMID: 21948316]. Pharmacological modulation of P-gp is therapeutically desirable but technically challenging due to the high risk of systemic drug-drug interactions and the potential for increased neurotoxicity of co-administered medications [FDA: Drug Development and Drug Interactions].

Other names

Multidrug resistance protein 1MDR1P-glycoprotein 1CD243ABC20P-glycoprotein

ATP-dependent efflux pump that transports substrates from the intracellular or intramembrane space to the extracellular environment against a concentration gradient.