Functional expression and localization of P-glycoprotein in the central nervous system: relevance to the pathogenesis and treatment of neurological disorders.
The expression of membrane drug transport systems in the central nervous system plays an important role in the brain disposition and efficacy of many pharmacological agents used in the treatment of neurological disorders such as neoplasia, epilepsy, and HIV-associated dementia. Of particular interest is P-glycoprotein, a membrane-associated, energy-dependent, efflux transporter that confers the multidrug resistance phenotype to many cells by extruding a broad range of xenobiotics from the cell, resulting in poor clinical outcomes. In addition, the expression pattern of P-glycoprotein has recently been suggested to play a key role in the etiology and pathogenesis of certain diseases such as Alzheimer's and Parkinson's diseases. This review will focus on the cellular localization, molecular expression, and functional activity of P-glycoprotein in several compartments of the central nervous system and address its relevance in the pathogenesis and pharmacological treatment of neurological disorders.
Lee
Gloria
G
Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario M5S 2S2, Canada.
Bendayan
Reina
R
D015526:AIDS Dementia Complex / Q000378:metabolism; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000648:ultrastructure; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D006801:Humans; D010300:Parkinson Disease / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1