ArticleCurrent Alzheimer research2015
The ATP-Binding Cassette Transporter-2 (ABCA2) Overexpression Modulates Sphingosine Levels and Transcription of the Amyloid Precursor Protein (APP) Gene.
Article in Current Alzheimer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Lipid transport mechanisms in human ABCA family transporters: a structural perspective.Biochemical Society transactions · 2026Review
- Multi-omics profiling implicates gut microbiota-sphingolipid interplay in the neuroprotective effects of semaglutide on diabetic cognitive impairment.Frontiers in microbiology · 2026Article
- Characterization of the phenotype and function of PRELPFrontiers in genetics · 2025Article
- Role of sphingolipid metabolites in the homeostasis of steroid hormones and the maintenance of testicular functions.Frontiers in endocrinology · 2023Review
- Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer's Disease.Biomedicines · 2022Article
- Protein kinase C regulates organic anion transporter 1 through phosphorylating ubiquitin ligase Nedd4-2.BMC molecular and cell biology · 2021Article
- Uncurtaining the pivotal role of ABC transporters in diabetes mellitus.Environmental science and pollution research international · 2021Review
- The Interplay of ABC Transporters in Aβ Translocation and Cholesterol Metabolism: Implicating Their Roles in Alzheimer's Disease.Molecular neurobiology · 2021Review
- Strategies to gain novel Alzheimer's disease diagnostics and therapeutics using modulators of ABCA transporters.Free neuropathology · 2021Article
- Elusive Roles of the Different Ceramidases in Human Health, Pathophysiology, and Tissue Regeneration.Cells · 2020Review
- Impairment of amyloid precursor protein alpha-processing in cerebral microvessels of type 1 diabetic mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
- Age-Related Functional and Expressional Changes in Efflux Pathways at the Blood-Brain Barrier.Frontiers in aging neuroscience · 2019Article
- ATP-binding cassette transporter-2 (ABCA2) as a therapeutic target.Biochemical pharmacology · 2018Review
- ATP Binding Cassette Subfamily A Member 2 (ABCA2) Expression and Methylation are Associated with Alzheimer's Disease.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Unraveling the genes implicated in Alzheimer's disease.Biomedical reports · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
The ATP-binding cassette transporter-2 (ABCA2) is a member of a family of multipass transmembrane proteins that use the energy of ATP hydrolysis to transport substrates across membrane bilayers. ABCA2 has also been genetically linked with Alzheimer's disease but the molecular mechanisms are unknown. In this report, we hypothesized that ABCA2 modulation of sphingolipid metabolism activates a signaling pathway that regulates amyloid precursor protein transcription. We found that ABCA2 overexpression in N2a cells was associated with increased mass of the sphingolipid sphingosine, derived from the catabolism of ceramide. ABCA2 overexpression increased in vitro alkaline and acid ceramidase activity. Sphingosine is a physiological inhibitor of protein kinase C (PKC) activity. Pharmacological inhibition of ceramidase activity or activation PKC activity with 12-myristate 13-acetate (PMA) or diacylglycerol (DAG) decreased endogenous APP mRNA levels in ABCA2 overexpressing cells. Treatment with PMA also decreased the expression of a transfected human APP promoter reporter construct, while treatment with a general PKC inhibitor, GF109203x, increased APP promoter activity. In N2a cells, chromatin immunoprecipitation experiments revealed that a repressive complex forms at the AP-1 site in the human APP promoter, consisting of c-jun, c-jun dimerization protein 2 (JDP2) and HDAC3 and this complex was reduced in ABCA2 overexpressing cells. Activation of the human APP promoter in A2 cells was directed by the upstream stimulatory factors USF-1 and USF-2 that bound to an E-box element in vivo. These findings indicate that ABCA2 overexpression modulates sphingosine levels and regulates transcription of the endogenous APP gene.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.