Abstract
Membrane-associated drug transporters are important determinants of antiretroviral drug disposition in the central nervous system during HIV-1 infection. A number of influx and efflux transport proteins expressed at the blood-brain barrier, blood-cerebrospinal fluid barrier and in brain parenchyma cellular compartments (i.e., astrocytes, microglia) have been implicated in the traffic of many antiretroviral drugs into and out of the brain. In particular, members of the ATP-binding cassette membrane associated transporter superfamily and Solute Carrier family are known to be involved in the efflux and/or influx of drugs, respectively. As a result, changes in the functional expression of these transporters can alter the disposition and distribution of drugs in the brain. Moreover, antiretroviral therapy itself and/or pathological events (i.e., inflammation, oxidative stress) associated with viral infection may affect the functional expression of these transporters. This review summarizes recent knowledge on the role of drug transporters in regulating brain antiretroviral drug transport in the context of HIV-1 infection.
Keywords: HIV-1, brain, drug transport, ABC transporter, SLC transporter, antiretroviral drugs, neuropathogenesis.
Current Pharmaceutical Design
Title:Role of CNS Transporters in the Pharmacotherapy of HIV-1 Associated Neurological Disorders
Volume: 20 Issue: 10
Author(s): Tamima Ashraf, Kevin Robillard, Gary N.Y. Chan and Reina Bendayan
Affiliation:
Keywords: HIV-1, brain, drug transport, ABC transporter, SLC transporter, antiretroviral drugs, neuropathogenesis.
Abstract: Membrane-associated drug transporters are important determinants of antiretroviral drug disposition in the central nervous system during HIV-1 infection. A number of influx and efflux transport proteins expressed at the blood-brain barrier, blood-cerebrospinal fluid barrier and in brain parenchyma cellular compartments (i.e., astrocytes, microglia) have been implicated in the traffic of many antiretroviral drugs into and out of the brain. In particular, members of the ATP-binding cassette membrane associated transporter superfamily and Solute Carrier family are known to be involved in the efflux and/or influx of drugs, respectively. As a result, changes in the functional expression of these transporters can alter the disposition and distribution of drugs in the brain. Moreover, antiretroviral therapy itself and/or pathological events (i.e., inflammation, oxidative stress) associated with viral infection may affect the functional expression of these transporters. This review summarizes recent knowledge on the role of drug transporters in regulating brain antiretroviral drug transport in the context of HIV-1 infection.
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Cite this article as:
Ashraf Tamima, Robillard Kevin, Chan N.Y. Gary and Bendayan Reina, Role of CNS Transporters in the Pharmacotherapy of HIV-1 Associated Neurological Disorders, Current Pharmaceutical Design 2014; 20 (10) . https://dx.doi.org/10.2174/13816128113199990464
DOI https://dx.doi.org/10.2174/13816128113199990464 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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