ArticleNature communications2018
Neuronal lysosomal dysfunction releases exosomes harboring APP C-terminal fragments and unique lipid signatures.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers.
What it found
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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
138 citing papers in PubMed, 215 citations in OpenAlex.
- Renal stress-associated extracellular vesicle signaling linked to lysosomal cathepsin D and NEK7-NLRP3 neuroinflammation.Molecular biomedicine · 2026Article
- Hemifusomes and proteolipid nanodroplets: a critical synthesis of an emerging model for endosomal membrane remodeling.Cell communication and signaling : CCS · 2026Review
- Local autophagy impairment triggers brain-wide presynaptic remodeling and resilience.The EMBO journal · 2026Article
- Exosome Biology at the Interface of Neurodegeneration and Therapeutic Innovation.Molecular neurobiology · 2026Review
- Palmitic acid-induced autolysosomal dysfunction and lipotoxicity in neuroinflammation and neurodegeneration.Neural regeneration research · 2026Article
- Neurodegenerative NMNAT2 Deficiency Promotes APP Processing in a SARM1-Dependent Manner.Cells · 2026Article
- SEC14L2 couples chaperone-mediated autophagy to microtubule stability by targeting Stathmin 1.Nature communications · 2026Article
- Review
- Pathogenic variants in BORCS5 cause a spectrum of neurodevelopmental and neurodegenerative disorders with lysosomal dysfunction.The Journal of clinical investigation · 2026Article
- Small Extracellular Vesicles from Neural Cells: Physiological and Pathological Roles, and Potential in Neurodegenerative Therapy.Advanced healthcare materials · 2026Review
- Valosin-containing protein is cargo in Amyloid Precursor Protein extracellular vesicles.Cell communication and signaling : CCS · 2026Article
- NDST3 suppression restores lysosomal acidification and ameliorates amyloid-β and MAPT/tau pathology in Alzheimer's disease.Translational neurodegeneration · 2026Article
- Restoration of lysosomal membrane integrity in cell models of Pompe disease depends on fatty acid synthase and its product palmitic acid.Cellular & molecular biology letters · 2026Article
- Lipid Messengers: Mechanisms and Clinical Applications of Exosomal Lipids in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Synergistic Upregulation of Extracellular Vesicles and Cell-Free Nucleic Acids by Chloroquine and Temozolomide in Glioma Cell Cultures.International journal of molecular sciences · 2025Article
- CLN5 deficiency impairs glucose uptake and uncovers PHGDH as a potential biomarker in Batten disease.Molecular psychiatry · 2025Article
- LRRK2 kinase activity regulates Parkinson's disease-relevant lipids at the lysosome.Molecular neurodegeneration · 2025Article
- Review
- The PKCι-β-arrestin2 axis disrupts SORLA retrograde trafficking, driving its degradation and amyloid pathology in Alzheimer's disease.Molecular neurodegeneration · 2025Article
- Extracellular Vesicles in the Crosstalk of Autophagy and Apoptosis: A Role for Lipid Rafts.Cells · 2025Review
78 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Defects in endolysosomal and autophagic functions are increasingly viewed as key pathological features of neurodegenerative disorders. A master regulator of these functions is phosphatidylinositol-3-phosphate (PI3P), a phospholipid synthesized primarily by class III PI 3-kinase Vps34. Here we report that disruption of neuronal Vps34 function in vitro and in vivo impairs autophagy, lysosomal degradation as well as lipid metabolism, causing endolysosomal membrane damage. PI3P deficiency also promotes secretion of unique exosomes enriched for undigested lysosomal substrates, including amyloid precursor protein C-terminal fragments (APP-CTFs), specific sphingolipids, and the phospholipid bis(monoacylglycero)phosphate (BMP), which normally resides in the internal vesicles of endolysosomes. Secretion of these exosomes requires neutral sphingomyelinase 2 and sphingolipid synthesis. Our results reveal a homeostatic response counteracting lysosomal dysfunction via secretion of atypical exosomes eliminating lysosomal waste and define exosomal APP-CTFs and BMP as candidate biomarkers for endolysosomal dysfunction associated with neurodegenerative disorders.
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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.