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ABC Transporter C1 Prevents Dimethyl Fumarate from Targeting Alzheimer's Disease

Möhle, Luisa ; Stefan, Katja ; Bascuñana, Pablo ; Brackhan, Mirjam ; Brüning, Thomas ; Eiriz, Ivan ; El Menuawy, Ahmed ; van Genderen, Sylvie ; Santos-García, Irene ; Górska, Anna Maria ; Villa, María ; Wu, Jingyun ; Stefan, Sven Marcel ; Pahnke, Jens

Biology (Basel, Switzerland), 2023-06, Vol.12 (7), p.932 [Periódico revisado por pares]

Switzerland: MDPI AG

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Título:
ABC Transporter C1 Prevents Dimethyl Fumarate from Targeting Alzheimer's Disease
Autor: Möhle, Luisa ; Stefan, Katja ; Bascuñana, Pablo ; Brackhan, Mirjam ; Brüning, Thomas ; Eiriz, Ivan ; El Menuawy, Ahmed ; van Genderen, Sylvie ; Santos-García, Irene ; Górska, Anna Maria ; Villa, María ; Wu, Jingyun ; Stefan, Sven Marcel ; Pahnke, Jens
Assuntos: ABC transporter ; ABC transporters ; AD mouse model ; Alzheimer's disease ; Amyloidosis ; Animal cognition ; Brain research ; Cell culture ; Dementia ; Dementia disorders ; dimethyl fumarate ; DMF ; Drinking water ; Drug development ; drug repurposing ; Drugs ; Ethylenediaminetetraacetic acid ; Genetic engineering ; Glutathione ; Health aspects ; International economic relations ; Ketamine ; Multiple sclerosis ; Neurodegenerative diseases ; Pharmaceutical industry ; Proteins ; β-Amyloid
É parte de: Biology (Basel, Switzerland), 2023-06, Vol.12 (7), p.932
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
HSØ/2019054
Current address: Department of Neuroscience, Instituto de Investigación Sanitaria del Hospital Universitario La Paz, 28046 Madrid, Spain.
These authors contributed equally to this work.
Current address: Department of Nuclear Medicine, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, 28040 Madrid, Spain.
Current address: Institute for Breeding Research on Horticultural Crops, Julius-Kühn-Institute (JKI)—Federal Research Centre for Cultivated Plants, 06484 Quedlinburg, Germany.
Descrição: 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.
Editor: Switzerland: MDPI AG
Idioma: Inglês;Norueguês

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ABC Transporter C1 Prevents Dimethyl Fumarate from Targeting Alzheimer's Disease

Möhle, Luisa ; Stefan, Katja ; Bascuñana, Pablo ; Brackhan, Mirjam ; Brüning, Thomas ; Eiriz, Ivan ; El Menuawy, Ahmed ; van Genderen, Sylvie ; Santos-García, Irene ; Górska, Anna Maria ; Villa, María ; Wu, Jingyun ; Stefan, Sven Marcel ; Pahnke, Jens

Switzerland: MDPI AG

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