ABC Transporter C1 Prevents Dimethyl Fumarate from Targeting Alzheimer’s Disease
Alzheimer’s disease (AD), the leading cause of dementia, is a growing health issue with very limited treatment options. To meet the need for novel therapeutics, existing drugs with additional preferred pharmacological profiles could be recruited. This strategy is known as ‘drug repurposing’. Here, w...
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| Format: | Article |
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MDPI AG
2023-06-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/12/7/932 |
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| author | Luisa Möhle Katja Stefan Pablo Bascuñana Mirjam Brackhan Thomas Brüning Ivan Eiriz Ahmed El Menuawy Sylvie van Genderen Irene Santos-García Anna Maria Górska María Villa Jingyun Wu Sven Marcel Stefan Jens Pahnke |
| author_facet | Luisa Möhle Katja Stefan Pablo Bascuñana Mirjam Brackhan Thomas Brüning Ivan Eiriz Ahmed El Menuawy Sylvie van Genderen Irene Santos-García Anna Maria Górska María Villa Jingyun Wu Sven Marcel Stefan Jens Pahnke |
| author_sort | Luisa Möhle |
| collection | DOAJ |
| description | Alzheimer’s disease (AD), the leading cause of dementia, is a growing health issue with very limited treatment options. To meet the need for novel therapeutics, existing drugs with additional preferred pharmacological profiles could be recruited. This strategy is known as ‘drug repurposing’. 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 β-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 β-amyloid (Aβ) deposition. We found that DMF treatment did not result in modulating effects on Aβ 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–brain and blood–plexus barriers and a key player for Aβ 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. |
| first_indexed | 2024-03-11T01:17:54Z |
| format | Article |
| id | doaj.art-b3743d71a7f84bc691a9e0438153a5e3 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-11T01:17:54Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-b3743d71a7f84bc691a9e0438153a5e32023-11-18T18:23:15ZengMDPI AGBiology2079-77372023-06-0112793210.3390/biology12070932ABC Transporter C1 Prevents Dimethyl Fumarate from Targeting Alzheimer’s DiseaseLuisa Möhle0Katja Stefan1Pablo Bascuñana2Mirjam Brackhan3Thomas Brüning4Ivan Eiriz5Ahmed El Menuawy6Sylvie van Genderen7Irene Santos-García8Anna Maria Górska9María Villa10Jingyun Wu11Sven Marcel Stefan12Jens Pahnke13Department of Pathology, Section of Neuropathology/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, NorwayDepartment of Pathology, Section of Neuropathology/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, NorwayDepartment of Pathology, Section of Neuropathology/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, NorwayDepartment of Pathology, Section of Neuropathology/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, NorwayDepartment of Pathology, Section of Neuropathology/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, NorwayDepartment of Pathology, Section of Neuropathology/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, NorwayDepartment of Pathology, Section of Neuropathology/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, NorwayDepartment of Pathology, Section of Neuropathology/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, NorwayDepartment of Pathology, Section of Neuropathology/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, NorwayDepartment of Pathology, Section of Neuropathology/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, NorwayDepartment of Pathology, Section of Neuropathology/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, NorwayDepartment of Pathology, Section of Neuropathology/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, NorwayDepartment of Pathology, Section of Neuropathology/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, NorwayDepartment of Pathology, Section of Neuropathology/Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, NorwayAlzheimer’s disease (AD), the leading cause of dementia, is a growing health issue with very limited treatment options. To meet the need for novel therapeutics, existing drugs with additional preferred pharmacological profiles could be recruited. This strategy is known as ‘drug repurposing’. 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 β-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 β-amyloid (Aβ) deposition. We found that DMF treatment did not result in modulating effects on Aβ 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–brain and blood–plexus barriers and a key player for Aβ 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.https://www.mdpi.com/2079-7737/12/7/932dimethyl fumarateDMFAlzheimer’s diseaseAD mouse modeldrug repurposingmultiple sclerosis |
| spellingShingle | Luisa Möhle Katja Stefan Pablo Bascuñana Mirjam Brackhan Thomas Brüning Ivan Eiriz Ahmed El Menuawy Sylvie van Genderen Irene Santos-García Anna Maria Górska María Villa Jingyun Wu Sven Marcel Stefan Jens Pahnke ABC Transporter C1 Prevents Dimethyl Fumarate from Targeting Alzheimer’s Disease Biology dimethyl fumarate DMF Alzheimer’s disease AD mouse model drug repurposing multiple sclerosis |
| title | ABC Transporter C1 Prevents Dimethyl Fumarate from Targeting Alzheimer’s Disease |
| title_full | ABC Transporter C1 Prevents Dimethyl Fumarate from Targeting Alzheimer’s Disease |
| title_fullStr | ABC Transporter C1 Prevents Dimethyl Fumarate from Targeting Alzheimer’s Disease |
| title_full_unstemmed | ABC Transporter C1 Prevents Dimethyl Fumarate from Targeting Alzheimer’s Disease |
| title_short | ABC Transporter C1 Prevents Dimethyl Fumarate from Targeting Alzheimer’s Disease |
| title_sort | abc transporter c1 prevents dimethyl fumarate from targeting alzheimer s disease |
| topic | dimethyl fumarate DMF Alzheimer’s disease AD mouse model drug repurposing multiple sclerosis |
| url | https://www.mdpi.com/2079-7737/12/7/932 |
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