P-glycoprotein expression and function are increased in an animal model of amyotrophic lateral sclerosis
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 ap...
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| مؤلفون آخرون: | , , , , , , |
| التنسيق: | article |
| منشور في: |
2010
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| الوصول للمادة أونلاين: | http://hdl.handle.net/10725/4497 http://dx.doi.org/10.1016/j.neulet.2010.01.078 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php http://www.sciencedirect.com/science/article/pii/S030439401000131X |
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| _version_ | 1864513463679713280 |
|---|---|
| author | Milane, Aline |
| author2 | Fernandez, Christine Dupuis, Luc Buyse, Marion Loeffler, Jean-Philippe Farinotti, Robert Meininger, Vincent Bensimon, Gilbert |
| author2_role | author author author author author author author |
| author_facet | Milane, Aline Fernandez, Christine Dupuis, Luc Buyse, Marion Loeffler, Jean-Philippe Farinotti, Robert Meininger, Vincent Bensimon, Gilbert |
| author_role | author |
| dc.creator.none.fl_str_mv | Milane, Aline Fernandez, Christine Dupuis, Luc Buyse, Marion Loeffler, Jean-Philippe Farinotti, Robert Meininger, Vincent Bensimon, Gilbert |
| dc.date.none.fl_str_mv | 2010 2016-10-04T09:39:20Z 2016-10-04T09:39:20Z 2016-10-04 |
| dc.identifier.none.fl_str_mv | 0304-3940 http://hdl.handle.net/10725/4497 http://dx.doi.org/10.1016/j.neulet.2010.01.078 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. http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php http://www.sciencedirect.com/science/article/pii/S030439401000131X |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | Neuroscience Letters |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | P-glycoprotein expression and function are increased in an animal model of amyotrophic lateral sclerosis |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_5f92b8cf4dd7f0df3058c7b3e2a8a851 |
| identifier_str_mv | 0304-3940 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. |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/4497 |
| publishDate | 2010 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | P-glycoprotein expression and function are increased in an animal model of amyotrophic lateral sclerosisMilane, AlineFernandez, ChristineDupuis, LucBuyse, MarionLoeffler, Jean-PhilippeFarinotti, RobertMeininger, VincentBensimon, GilbertThe 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.PublishedN/A2016-10-04T09:39:20Z2016-10-04T09:39:20Z20102016-10-04Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article0304-3940http://hdl.handle.net/10725/4497http://dx.doi.org/10.1016/j.neulet.2010.01.078Milane, 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.http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.phphttp://www.sciencedirect.com/science/article/pii/S030439401000131XenNeuroscience Lettersinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/44972021-03-19T10:03:18Z |
| spellingShingle | P-glycoprotein expression and function are increased in an animal model of amyotrophic lateral sclerosis Milane, Aline |
| status_str | publishedVersion |
| title | P-glycoprotein expression and function are increased in an animal model of amyotrophic lateral sclerosis |
| title_full | P-glycoprotein expression and function are increased in an animal model of amyotrophic lateral sclerosis |
| title_fullStr | P-glycoprotein expression and function are increased in an animal model of amyotrophic lateral sclerosis |
| title_full_unstemmed | P-glycoprotein expression and function are increased in an animal model of amyotrophic lateral sclerosis |
| title_short | P-glycoprotein expression and function are increased in an animal model of amyotrophic lateral sclerosis |
| title_sort | P-glycoprotein expression and function are increased in an animal model of amyotrophic lateral sclerosis |
| url | http://hdl.handle.net/10725/4497 http://dx.doi.org/10.1016/j.neulet.2010.01.078 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php http://www.sciencedirect.com/science/article/pii/S030439401000131X |