Luisa Möhle, Katja Stefan, Pablo Bascuñana, Mirjam Brackhan, Thomas Brüning, Ivan Eiriz, Ahmed El Menuawy 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

  • General Agricultural and Biological Sciences
  • General Immunology and Microbiology
  • General Biochemistry, Genetics and Molecular Biology
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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.

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