ArticleFEBS open bio2015
Analysis by a highly sensitive split luciferase assay of the regions involved in APP dimerization and its impact on processing.
Article in FEBS open bio, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Cholesterol-dependent amyloid β production: space for multifarious interactions between amyloid precursor protein, secretases, and cholesterol.Cell & bioscience · 2023Review
- Structural Determinant of β-Amyloid Formation: From Transmembrane Protein Dimerization to β-Amyloid Aggregates.Biomedicines · 2022Review
- Knockdown of Amyloid Precursor Protein: Biological Consequences and Clinical Opportunities.Frontiers in neuroscience · 2022Review
- Cholesterol as a key player in amyloid β-mediated toxicity in Alzheimer's disease.Frontiers in molecular neuroscience · 2022Review
- Amyloid precursor protein (APP) and amyloid β (Aβ) interact with cell adhesion molecules: Implications in Alzheimer's disease and normal physiology.Frontiers in cell and developmental biology · 2022Review
- Rapid evolution of mammalian APLP1 as a synaptic adhesion molecule.Scientific reports · 2021Article
- Cholesterol-lowering drugs reduce APP processing to Aβ by inducing APP dimerization.Molecular biology of the cell · 2021Article
- Cholesterol and Alzheimer's Disease; From Risk Genes to Pathological Effects.Frontiers in aging neuroscience · 2021Review
- Bicelles Rich in both Sphingolipids and Cholesterol and Their Use in Studies of Membrane Proteins.Journal of the American Chemical Society · 2020Article
- Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor (LATS) Biosensor.Journal of visualized experiments : JoVE · 2018Article
- Bexarotene Binds to the Amyloid Precursor Protein Transmembrane Domain, Alters Its α-Helical Conformation, and Inhibits γ-Secretase Nonselectively in Liposomes.ACS chemical neuroscience · 2018Article
- Dimerization leads to changes in APP (amyloid precursor protein) trafficking mediated by LRP1 and SorLA.Cellular and molecular life sciences : CMLS · 2018Article
- Navβ2 knockdown improves cognition in APP/PS1 mice by partially inhibiting seizures and APP amyloid processing.Oncotarget · 2017Article
- Dimerization of the transmembrane domain of amyloid precursor protein is determined by residues around the γ-secretase cleavage sites.The Journal of biological chemistry · 2017Article
- Study on Lentivirus-Mediated ABCA7 Improves Neurocognitive Function and Related Mechanisms in the C57BL/6 Mouse Model of Alzheimer's Disease.Journal of molecular neuroscience : MN · 2017Article
- Structural and biochemical differences between the Notch and the amyloid precursor protein transmembrane domains.Science advances · 2017Article
- Impact of membrane lipid composition on the structure and stability of the transmembrane domain of amyloid precursor protein.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Glycines from the APP GXXXG/GXXXA Transmembrane Motifs Promote Formation of Pathogenic Aβ Oligomers in Cells.Frontiers in aging neuroscience · 2016Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Alzheimer's disease (AD) is a neurodegenerative disease that causes progressive loss of cognitive functions, leading to dementia. Two types of lesions are found in AD brains: neurofibrillary tangles and senile plaques. The latter are composed mainly of the β-amyloid peptide (Aβ) generated by amyloidogenic processing of the amyloid precursor protein (APP). Several studies have suggested that dimerization of APP is closely linked to Aβ production. Nevertheless, the mechanisms controlling APP dimerization and their role in APP function are not known. Here we used a new luciferase complementation assay to analyze APP dimerization and unravel the involvement of its three major domains: the ectodomain, the transmembrane domain and the intracellular domain. Our results indicate that within cells full-length APP dimerizes more than its α and β C-terminal fragments, confirming the pivotal role of the ectodomain in this process. Dimerization of the APP transmembrane (TM) domain has been reported to regulate processing at the γ-cleavage site. We show that both non-familial and familial AD mutations in the TM GXXXG motifs strongly modulate Aβ production, but do not consistently change dimerization of the C-terminal fragments. Finally, we found for the first time that removal of intracellular domain strongly increases APP dimerization. Increased APP dimerization is linked to increased non-amyloidogenic processing.
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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.