ArticleThe Journal of biological chemistry2009
Neuroprotective secreted amyloid precursor protein acts by disrupting amyloid precursor protein dimers.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 139 citations in OpenAlex.
- Inducers and modulators of protein aggregation in Alzheimer's disease - Critical tools for understanding the foundations of aggregate structures.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Comparative Single-Cell Transcriptomics of Human Neuroblastoma and Preclinical Models Reveals Conservation of an Adrenergic Cell State.Cancer research · 2025Article
- Cholesterol-dependent amyloid β production: space for multifarious interactions between amyloid precursor protein, secretases, and cholesterol.Cell & bioscience · 2023Review
- Amyloid precursor protein and its interacting proteins in neurodevelopment.Biochemical Society transactions · 2023Review
- APP family member dimeric complexes are formed predominantly in synaptic compartments.Cell & bioscience · 2023Article
- The brain on time: links between development and neurodegeneration.Development (Cambridge, England) · 2023Article
- Double Mutations in a Patient with Early-Onset Alzheimer's Disease in Korea: AnInternational journal of molecular sciences · 2023Article
- The Binding of Different Substrate Molecules at the Docking Site and the Active Site of γ-Secretase Can Trigger Toxic Events in Sporadic and Familial Alzheimer's Disease.International journal of molecular sciences · 2023Article
- Necroptosis and Alzheimer's Disease: Pathogenic Mechanisms and Therapeutic Opportunities.Journal of Alzheimer's disease : JAD · 2023Review
- Targeting heparan sulfate-protein interactions with oligosaccharides and monoclonal antibodies.Frontiers in molecular biosciences · 2023Review
- The Heparanase Regulatory Network in Health and Disease.International journal of molecular sciences · 2021Review
- Rho-associated kinases contribute to the regulation of tau phosphorylation and amyloid metabolism during neuronal plasticity.Pharmacological reports : PR · 2021Article
- Fluorescence-based techniques for the detection of the oligomeric status of proteins: implication in amyloidogenic diseases.European biophysics journal : EBJ · 2021Review
- Pharmacologic Inhibition of ADAM10 Attenuates Brain Tissue Loss, Axonal Injury and Pro-inflammatory Gene Expression Following Traumatic Brain Injury in Mice.Frontiers in cell and developmental biology · 2021Article
- Gallic acid is a dual α/β-secretase modulator that reverses cognitive impairment and remediates pathology in Alzheimer mice.The Journal of biological chemistry · 2020Article
- Effect of Aβ Oligomers on Neuronal APP Triggers a Vicious Cycle Leading to the Propagation of Synaptic Plasticity Alterations to Healthy Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- L-histidine and L-carnosine exert anti-brain aging effects in D-galactose-induced aged neuronal cells.Nutrition research and practice · 2020Article
- New Insights Into Blood-Brain Barrier Maintenance: The Homeostatic Role of β-Amyloid Precursor Protein in Cerebral Vasculature.Frontiers in physiology · 2020Review
- Mechanisms of action of amyloid-beta and its precursor protein in neuronal cell death.Metabolic brain disease · 2020Review
- Beyond the Ligand: Extracellular and Transcellular G Protein-Coupled Receptor Complexes in Physiology and Pharmacology.Pharmacological reviews · 2019Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The amyloid precursor protein (APP) is implied both in cell growth and differentiation and in neurodegenerative processes in Alzheimer disease. Regulated proteolysis of APP generates biologically active fragments such as the neuroprotective secreted ectodomain sAPPalpha and the neurotoxic beta-amyloid peptide. Furthermore, it has been suggested that the intact transmembrane APP plays a signaling role, which might be important for both normal synaptic plasticity and neuronal dysfunction in dementia. To understand APP signaling, we tracked single molecules of APP using quantum dots and quantitated APP homodimerization using fluorescence lifetime imaging microscopy for the detection of Förster resonance energy transfer in living neuroblastoma cells. Using selective labeling with synthetic fluorophores, we show that the dimerization of APP is considerably higher at the plasma membrane than in intracellular membranes. Heparan sulfate significantly contributes to the almost complete dimerization of APP at the plasma membrane. Importantly, this technique for the first time structurally defines the initiation of APP signaling by binding of a relevant physiological extracellular ligand; our results indicate APP as receptor for neuroprotective sAPPalpha, as sAPPalpha binding disrupts APP dimers, and this disruption of APP dimers by sAPPalpha is necessary for the protection of neuroblastoma cells against starvation-induced cell death. Only cells expressing reversibly dimerized wild-type, but not covalently dimerized mutant APP are protected by sAPPalpha. These findings suggest a potentially beneficial effect of increasing sAPPalpha production or disrupting APP dimers for neuronal survival.
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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.