ArticleCellular and molecular life sciences : CMLS2018
Dimerization leads to changes in APP (amyloid precursor protein) trafficking mediated by LRP1 and SorLA.
Article in Cellular and molecular life sciences : CMLS, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 42 citations in OpenAlex.
- Delineating the Role of GxxxG Motif in Amyloidogenesis: A New Perspective in Targeting Amyloid-Beta Mediated AD Pathogenesis.ACS bio & med chem Au · 2024Review
- Cholesterol-dependent amyloid β production: space for multifarious interactions between amyloid precursor protein, secretases, and cholesterol.Cell & bioscience · 2023Review
- APP family member dimeric complexes are formed predominantly in synaptic compartments.Cell & bioscience · 2023Article
- Alternative splicing in neurodegenerative disease and the promise of RNA therapies.Nature reviews. Neuroscience · 2023Review
- Differential effects of familial Alzheimer's disease-causing mutations on amyloid precursor protein (APP) trafficking, proteolytic conversion, and synaptogenic activity.Acta neuropathologica communications · 2023Article
- Structural Determinant of β-Amyloid Formation: From Transmembrane Protein Dimerization to β-Amyloid Aggregates.Biomedicines · 2022Review
- The adaptor protein PICK1 targets the sorting receptor SorLA.Molecular brain · 2022Article
- Voluntary wheel running alters markers of amyloid-beta precursor protein processing in an ovarian hormone depleted model.Frontiers in endocrinology · 2022Article
- The apolipoprotein receptor LRP3 compromises APP levels.Alzheimer's research & therapy · 2021Article
- Review
- 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
- Alteration in synaptic nanoscale organization dictates amyloidogenic processing in Alzheimer's disease.iScience · 2021Article
- Cholesterol and Alzheimer's Disease; From Risk Genes to Pathological Effects.Frontiers in aging neuroscience · 2021Review
- Dimeric Transmembrane Orientations of APP/C99 Regulate γ-Secretase Processing Line Impacting Signaling and Oligomerization.iScience · 2020Article
- The Rab5 activator RME-6 is required for amyloid precursor protein endocytosis depending on the YTSI motif.Cellular and molecular life sciences : CMLS · 2020Article
- Determining the Protein Stability of Alzheimer's Disease Protein, Amyloid Precursor Protein.The protein journal · 2019Article
- CD2-associated protein (CD2AP) overexpression accelerates amyloid precursor protein (APP) transfer from early endosomes to the lysosomal degradation pathway.The Journal of biological chemistry · 2019Article
- Melting Down Protein Stability: PAPS Synthase 2 in Patients and in a Cellular Environment.Frontiers in molecular biosciences · 2019Review
- Trafficking in Alzheimer's Disease: Modulation of APP Transport and Processing by the Transmembrane Proteins LRP1, SorLA, SorCS1c, Sortilin, and Calsyntenin.Molecular neurobiology · 2018Review
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
Proteolytic cleavage of the amyloid precursor protein (APP) by α-, β- and γ-secretases is a determining factor in Alzheimer's disease (AD). Imbalances in the activity of all three enzymes can result in alterations towards pathogenic Aβ production. Proteolysis of APP is strongly linked to its subcellular localization as the secretases involved are distributed in different cellular compartments. APP has been shown to dimerize in cis-orientation, affecting Aβ production. This might be explained by different substrate properties defined by the APP oligomerization state or alternatively by altered APP monomer/dimer localization. We investigated the latter hypothesis using two different APP dimerization systems in HeLa cells. Dimerization caused a decreased localization of APP to the Golgi and at the plasma membrane, whereas the levels in the ER and in endosomes were increased. Furthermore, we observed via live cell imaging and biochemical analyses that APP dimerization affects its interaction with LRP1 and SorLA, suggesting that APP dimerization modulates its interplay with sorting molecules and in turn its localization and processing. Thus, pharmacological approaches targeting APP oligomerization properties might open novel strategies for treatment of AD.
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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.