ArticleBMC molecular and cell biology2020
Alix and Syntenin-1 direct amyloid precursor protein trafficking into extracellular vesicles.
Article in BMC molecular and cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 48 citations in OpenAlex.
- CARM1-mediated hypoxanthine-enriched exosomes rewire inosine metabolism and impair CD8Cell death and differentiation · 2026Article
- Review
- Dengue virus harnesses mosquito Syntenin to load and secrete viral RNA into salivary exosomes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Extracellular Vesicles for Clinical Diagnostics: From Bulk Measurements to Single-Vesicle Analysis.ACS nano · 2025Review
- Tumor-derived exosomes and their application in cancer treatment.Journal of translational medicine · 2025Review
- Biogenesis and functional implications of extracellular vesicles in cancer metastasis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Enrichment of extracellular vesicles using Mag-Net for the analysis of the plasma proteome.Nature communications · 2025Article
- NEU1-Mediated Extracellular Vesicle Glycosylation in Alzheimer's Disease: Mechanistic Insights into Intercellular Communication and Therapeutic Targeting.Pharmaceuticals (Basel, Switzerland) · 2025Review
- ESCRT-I and PTPN23 mediate microautophagy of ubiquitylated tau aggregates.The Journal of cell biology · 2025Article
- ESCRT disruption provides evidence against trans-synaptic signaling via extracellular vesicles.The Journal of cell biology · 2024Article
- ESCRT disruption provides evidence against transsynaptic signaling functions for extracellular vesicles.bioRxiv : the preprint server for biology · 2024Article
- Mag-Net: Rapid enrichment of membrane-bound particles enables high coverage quantitative analysis of the plasma proteome.bioRxiv : the preprint server for biology · 2024Article
- Upscaling human mesenchymal stromal cell production in a novel vertical-wheel bioreactor enhances extracellular vesicle secretion and cargo profile.Bioactive materials · 2023Article
- The Multifunctional Protein Syntenin-1: Regulator of Exosome Biogenesis, Cellular Function, and Tumor Progression.International journal of molecular sciences · 2023Review
- Colorectal cancer-derived small extracellular vesicles induce TGFβ1-mediated epithelial to mesenchymal transition of hepatocytes.Cancer cell international · 2023Article
- The Potential Roles of Exosomes Carrying APP and Tau Cleavage Products in Alzheimer's Disease.Journal of clinical medicine · 2023Review
- Extracellular Vesicles as Novel Drug-Delivery Systems through Intracellular Communications.Membranes · 2022Review
- Circulating extracellular vesicles: friends and foes in neurodegeneration.Neural regeneration research · 2022Review
- Alzheimer's Disease-Related Genes Identified by Linking Spatial Patterns of Pathology and Gene Expression.Frontiers in neuroscience · 2022Article
- Extracellular Vesicle Collection from Human Stem Cells Grown in Suspension Bioreactors.Methods in molecular biology (Clifton, N.J.) · 2022Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEndosomal trafficking and amyloidogenic cleavage of amyloid precursor protein (APP) is believed to play a role in the neurodegeneration observed in Alzheimer's disease (AD). Recent evidence has suggested that packaging and secretion of APP and its amyloidogenic cleaved products into small extracellular vesicles (EVs) may facilitate uptake of these neurotoxic factors during disease progression. However, the molecular mechanisms underlying trafficking of APP into EVs are poorly understood.
resultsIn this study, the mechanism and impact of APP trafficking into extracellular vesicles (EVs) were assessed by a series of inducible gene knockdowns. We demonstrate that vesicle-associated proteins Alix and Syntenin-1 are essential for proper subcellular localization and efficient EV secretion of APP via an endosomal sorting complexes required for transport (ESCRT)-independent pathway. The neurotoxic C-terminal fragment (CTFβ) of APP is similarly secreted in association with small vesicles. These mechanisms are conserved in terminally differentiated neuron-like cells. Furthermore, knockdown of Alix and Syntenin-1 alters the subcellular localization of APP, sequestering the precursor protein to endoplasmic reticulum and endolysosomal compartments, respectively. Finally, transfer of small EVs containing mutant APP confers an increase in reactive oxygen species production and neurotoxicity to human induced pluripotent stem cell-derived cortical neurons and naïve primary neurons, an effect that is ameliorated by Alix and Syntenin-1 depletion.
conclusionsAltogether these findings elucidate a novel mechanism for understanding the intracellular trafficking of APP and CTFβ into secreted extracellular vesicles, and the resultant potential impact on neurotoxicity in the context of Alzheimer's disease amyloidopathy.
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