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To meet the need for novel therapeutics, existing drugs with additional preferred pharmacological profiles could be recruited. This strategy is known as \u2018drug repurposing\u2019. Here, we describe dimethyl fumarate (DMF), a drug approved to treat multiple sclerosis (MS), to be tested as a candidate for other brain diseases. We used an APP-transgenic model (APPtg) of senile \u03b2-amyloidosis mice to further investigate the potential of DMF as a novel AD therapeutic. We treated male and female APPtg mice through drinking water at late stages of \u03b2-amyloid (A\u03b2) deposition. We found that DMF treatment did not result in modulating effects on A\u03b2 deposition at this stage. Interestingly, we found that glutathione-modified DMF interacts with the ATP-binding cassette transporter ABCC1, an important gatekeeper at the blood\u2013brain and blood\u2013plexus barriers and a key player for A\u03b2 export from the brain. Our findings suggest that ABCC1 prevents the effects of DMF, which makes DMF unsuitable as a novel therapeutic drug against AD. The discovered effects of ABCC1 also have implications for DMF treatment of multiple sclerosis.<\/jats:p>","DOI":"10.3390\/biology12070932","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T01:17:46Z","timestamp":1688087866000},"page":"932","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["ABC Transporter C1 Prevents Dimethyl Fumarate from Targeting Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Luisa","family":"M\u00f6hle","sequence":"first","affiliation":[{"name":"Department of Pathology, Section of Neuropathology\/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katja","family":"Stefan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Neuropathology\/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Bascu\u00f1ana","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Neuropathology\/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirjam","family":"Brackhan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Neuropathology\/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7060-6564","authenticated-orcid":false,"given":"Thomas","family":"Br\u00fcning","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Neuropathology\/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Eiriz","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Neuropathology\/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"II","given":"Ahmed El Menuawy","family":"El Menuawy","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Neuropathology\/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvie","family":"van Genderen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Neuropathology\/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Santos-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Neuropathology\/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Maria","family":"G\u00f3rska","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Neuropathology\/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Villa","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Neuropathology\/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Neuropathology\/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2048-8598","authenticated-orcid":false,"given":"Sven Marcel","family":"Stefan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Neuropathology\/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway"},{"name":"Pahnke Lab (Drug Development and Chemical Biology), L\u00fcbeck Institute of Experimental Dermatology (LIED), University of L\u00fcbeck (UzL) and University Medical Center Schleswig-Holstein (UKSH), Ratzeburger Allee 160, 10 23538 L\u00fcbeck, Germany"},{"name":"School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7355-4213","authenticated-orcid":false,"given":"Jens","family":"Pahnke","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Neuropathology\/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway"},{"name":"Pahnke Lab (Drug Development and Chemical Biology), L\u00fcbeck Institute of Experimental Dermatology (LIED), University of L\u00fcbeck (UzL) and University Medical Center Schleswig-Holstein (UKSH), Ratzeburger Allee 160, 10 23538 L\u00fcbeck, Germany"},{"name":"Department of Pharmacology, Faculty of Medicine, University of Latvia, Jelgavas iela 3, 1004 R\u012bga, Latvia"},{"name":"Department of Neurobiology, The Georg S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2022). 2022 Alzheimer\u2019s disease facts and figures. Alzheimers Dement, 18, 700\u2013789.","DOI":"10.1002\/alz.12638"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/alzrt143","article-title":"Dementia: A global health priority\u2014Highlights from an ADI and World Health Organization report","volume":"4","author":"Wortmann","year":"2012","journal-title":"Alzheimer\u2019s Res. 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