ATP-binding cassette protein ABCA7 deficiency impairs sphingomyelin synthesis, cognitive discrimination, and synaptic plasticity in the entorhinal cortex.

ABSTRACT: Sphingomyelin (SM) is an abundant plasma membrane and plasma lipoprotein sphingolipid. We previously reported that ATP-binding cassette family A protein 1 (ABCA1) deficiency in humans and mice decreases plasma SM levels. However, overexpression, induction, downregulation, inhibition, and knockdown of ABCA1 in human hepatoma Huh7 cells did not decrease SM efflux. Using unbiased siRNA screening, here, we identified that ABCA7 plays a role in the biosynthesis and efflux of SM without affecting cellular uptake and metabolism. Since loss of function mutations in the ABCA7 gene exhibit strong associations with late-onset Alzheimer's disease across racial groups, we also studied the effects of ABCA7 deficiency in the mouse brain. Brains of ABCA7-deficient (KO) mice, compared with WT, had signific

SUBMITTER: Iqbal J 

PROVIDER: S-EPMC9513280 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature