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Adenosine triphosphate binding cassette subfamily C member 1 (ABCC1) overexpression reduces APP processing and increases alpha- versus beta-secretase activity, in vitro.

ABSTRACT: The organic anion transporter Adenosine triphosphate binding cassette subfamily C member 1 (ABCC1), also known as MRP1, has been demonstrated in murine models of Alzheimer's disease (AD) to export amyloid beta (Abeta) from the endothelial cells of the blood-brain barrier to the periphery, and that pharmaceutical activation of ABCC1 can reduce amyloid plaque deposition in the brain. Here, we show that ABCC1 is not only capable of exporting Abeta from the cytoplasm of human cells, but also that its overexpression significantly reduces Abeta production and increases the ratio of alpha- versus beta-secretase mediated cleavage of the amyloid precursor protein (APP), likely via indirect modulation of alpha-, beta- and gamma-secretase activity.

SUBMITTER: Jepsen WM 

PROVIDER: S-EPMC7860133 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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<i>Adenosine triphosphate binding cassette subfamily C member 1</i> (<i>ABCC1</i>) overexpression reduces APP processing and increases alpha- versus beta-secretase activity, <i>in vitro</i>.

Jepsen Wayne M WM   De Both Matthew M   Siniard Ashley L AL   Ramsey Keri K   Piras Ignazio S IS   Naymik Marcus M   Henderson Adrienne A   Huentelman Matthew J MJ  

Biology open 20210125 1

The organic anion transporter <i>Adenosine triphosphate binding cassette subfamily C member 1</i> (<i>ABCC1</i>), also known as <i>MRP1</i>, has been demonstrated in murine models of Alzheimer's disease (AD) to export amyloid beta (Abeta) from the endothelial cells of the blood-brain barrier to the periphery, and that pharmaceutical activation of <i>ABCC1</i> can reduce amyloid plaque deposition in the brain. Here, we show that ABCC1 is not only capable of exporting Abeta from the cytoplasm of h  ...[more]

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