P-glycoprotein expression and function are increased in an animal model of amyotrophic lateral sclerosis

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dc.contributor.author Milane, Aline
dc.contributor.author Fernandez, Christine
dc.contributor.author Dupuis, Luc
dc.contributor.author Buyse, Marion
dc.contributor.author Loeffler, Jean-Philippe
dc.contributor.author Farinotti, Robert
dc.contributor.author Meininger, Vincent
dc.contributor.author Bensimon, Gilbert
dc.date.accessioned 2016-10-04T09:39:20Z
dc.date.available 2016-10-04T09:39:20Z
dc.date.copyright 2010 en_US
dc.date.issued 2016-10-04
dc.identifier.issn 0304-3940 en_US
dc.identifier.uri http://hdl.handle.net/10725/4497
dc.description.abstract The efflux pumps located at the blood–brain barrier (BBB) prevent drugs entering the brain. As such, efflux pumps are a major obstacle to drug brain distribution. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with little therapeutics available: riluzole is the only drug approved in its treatment. The lack of response to treatment in ALS may be, at least in part, due to increased activities of efflux pumps in relation to disease, leading to subtherapeutic brain concentrations of drugs. In the present study, we used a transgenic mouse model of ALS (G86R mSOD1 mice) to test this hypothesis. Expression and functionality of P-glycoprotein (ABCB1, P-gp) and Breast Cancer Resistance Protein (ABCG2, BCRP), two major efflux pumps, were studied. We observed an increased P-gp expression (1.5-fold) in presymptomatic mSOD1 mice compared to wild-type controls. Consistent with this, P-gp function was also increased by 1.5-fold and riluzole brain disposition was decreased by 1.7-fold in mSOD1 mice. Contrasting with this, BCRP expression and function were unaltered by the pathology. These results demonstrate that BBB transport proteins are modified in G86R mSOD1 mice ALS model. Such findings underline potential problems in extrapolating the results of animal studies to humans and developing clinical trials, especially for drugs transported by P-gp. en_US
dc.language.iso en en_US
dc.title P-glycoprotein expression and function are increased in an animal model of amyotrophic lateral sclerosis en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SOP en_US
dc.author.idnumber 200904164 en_US
dc.author.department N/A en_US
dc.description.embargo N/A en_US
dc.relation.journal Neuroscience Letters en_US
dc.journal.volume 472 en_US
dc.journal.issue 3 en_US
dc.article.pages 166-170 en_US
dc.keywords Amyotrophic lateral sclerosis en_US
dc.keywords Blood–brain barrier en_US
dc.keywords mSOD1 mice en_US
dc.keywords P-glycoprotein en_US
dc.keywords BCRP en_US
dc.keywords Riluzole en_US
dc.identifier.doi http://dx.doi.org/10.1016/j.neulet.2010.01.078 en_US
dc.identifier.ctation Milane, A., Fernandez, C., Dupuis, L., Buyse, M., Loeffler, J. P., Farinotti, R., ... & Bensimon, G. (2010). P-glycoprotein expression and function are increased in an animal model of amyotrophic lateral sclerosis. Neuroscience letters, 472(3), 166-170. en_US
dc.author.email aline.milane@lau.edu.lb
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url http://www.sciencedirect.com/science/article/pii/S030439401000131X en_US

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