Abstract
Owing to therapeutic progress, the role of ABC-transporters in infectious and autoimmune inflammatory CNS-diseases has recently gained considerable attention. In HIV-encephalitis and HIV-associated neurocognitive disorders, ABC-transporters are discussed to contribute to limited CNS-penetration and -retention of antiviral agents. In multiple sclerosis and its animal model experimental autoimmune encephalomyelitis, ABC-transporters may be involved in pathogenesis and treatment response alike. A prospective pharmacogenetic study is currently underway to examine the predictive role of genetic variations in ABC-transporters for treatment response and adverse events to mitoxantrone, a therapeutic agent used in aggressive MS. These approaches may aid in individualized treatment with this cytostatic anthracenedione, addressing its narrow therapeutic index with potentially fatal side effects. Finally, understanding regulation and function of ABC-transporters under inflammatory conditions may also optimize ABC-transporter-related treatment strategies in other neurological diseases (e.g. neurodegenerative, and neurovascular) where neuroinflammatory mechanisms have gained considerable attention as important contributors to pathogenesis.
Keywords: multiple sclerosis, HIV-associated neurocognitive disorders, mitoxantrone, experimental autoimmune encephalomyelitis, cytokines, protease inhibitors, antiretroviral agents, biomarkers, mRNA-expression, drug metabolism
Current Pharmaceutical Design
Title: ATP-Binding Cassette Transporters in Inflammatory Brain Disease
Volume: 17 Issue: 26
Author(s): A. Chan, R. Gold and N. von Ahsen
Affiliation:
Keywords: multiple sclerosis, HIV-associated neurocognitive disorders, mitoxantrone, experimental autoimmune encephalomyelitis, cytokines, protease inhibitors, antiretroviral agents, biomarkers, mRNA-expression, drug metabolism
Abstract: Owing to therapeutic progress, the role of ABC-transporters in infectious and autoimmune inflammatory CNS-diseases has recently gained considerable attention. In HIV-encephalitis and HIV-associated neurocognitive disorders, ABC-transporters are discussed to contribute to limited CNS-penetration and -retention of antiviral agents. In multiple sclerosis and its animal model experimental autoimmune encephalomyelitis, ABC-transporters may be involved in pathogenesis and treatment response alike. A prospective pharmacogenetic study is currently underway to examine the predictive role of genetic variations in ABC-transporters for treatment response and adverse events to mitoxantrone, a therapeutic agent used in aggressive MS. These approaches may aid in individualized treatment with this cytostatic anthracenedione, addressing its narrow therapeutic index with potentially fatal side effects. Finally, understanding regulation and function of ABC-transporters under inflammatory conditions may also optimize ABC-transporter-related treatment strategies in other neurological diseases (e.g. neurodegenerative, and neurovascular) where neuroinflammatory mechanisms have gained considerable attention as important contributors to pathogenesis.
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Cite this article as:
Chan A., Gold R. and von Ahsen N., ATP-Binding Cassette Transporters in Inflammatory Brain Disease, Current Pharmaceutical Design 2011; 17 (26) . https://dx.doi.org/10.2174/138161211797440131
DOI https://dx.doi.org/10.2174/138161211797440131 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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