ArticleCellular and molecular life sciences : CMLS2020
Misfolded amyloid-β-42 impairs the endosomal-lysosomal pathway.
Article in Cellular and molecular life sciences : CMLS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 60 citations in OpenAlex.
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- Toxic mechanisms of amyloid oligomers and therapeutic strategies.Protein science : a publication of the Protein Society · 2026Review
- Altered trafficking of Kv1-Kvβ2 leads to neuronal hyperexcitability and memory deficits in amyloid-β pathology.Molecular neurodegeneration · 2026Article
- Lysosome trafficking across intracellular and intercellular networks in the brain.Frontiers in molecular neuroscience · 2026Article
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- Endocytic Pathways Unveil the Role of Syndecans in the Seeding and Spreading of Pathological Protein Aggregates: Insights into Neurodegenerative Disorders.International journal of molecular sciences · 2025Review
- Inhibition of amyloid beta oligomer accumulation by NU-9: A unifying mechanism for the treatment of neurodegenerative diseases.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Peony-shaped zinc oxide nanoflower synthesized via hydrothermal route exhibits promising anticancer and anti-amyloid activity.BMC pharmacology & toxicology · 2024Article
- A Novel 14mer Peptide Inhibits Autophagic Flux via Selective Activation of the mTORC1 Signalling Pathway: Implications for Alzheimer's Disease.International journal of molecular sciences · 2024Article
- Potential Mechanisms of Tunneling Nanotube Formation and Their Role in Pathology Spread in Alzheimer's Disease and Other Proteinopathies.International journal of molecular sciences · 2024Review
- Tailored Melatonin- and Donepezil-Based Hybrids Targeting Pathognomonic Changes in Alzheimer's Disease: An In Vitro and In Vivo Investigation.International journal of molecular sciences · 2024Article
- AβJournal of nanobiotechnology · 2024Article
- Insights from the neural guidance factor Netrin-1 into neurodegeneration and other diseases.Frontiers in molecular neuroscience · 2024Review
- Clathrin mediated endocytosis in Alzheimer's disease: cell type specific involvement in amyloid beta pathology.Frontiers in aging neuroscience · 2024Review
- Phosphorylation-state dependent intraneuronal sorting of Aβ differentially impairs autophagy and the endo-lysosomal system.Autophagy · 2024Article
- Therapeutic effects of a novel synthetic α-secretase.Frontiers in aging neuroscience · 2024Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Misfolding and aggregation of proteins is strongly linked to several neurodegenerative diseases, but how such species bring about their cytotoxic actions remains poorly understood. Here we used specifically-designed optical reporter probes and live fluorescence imaging in primary hippocampal neurons to characterise the mechanism by which prefibrillar, oligomeric forms of the Alzheimer's-associated peptide, Aβ42, exert their detrimental effects. We used a pH-sensitive reporter, Aβ42-CypHer, to track Aβ internalisation in real-time, demonstrating that oligomers are rapidly taken up into cells in a dynamin-dependent manner, and trafficked via the endo-lysosomal pathway resulting in accumulation in lysosomes. In contrast, a non-assembling variant of Aβ42 (vAβ42) assayed in the same way is not internalised. Tracking ovalbumin uptake into cells using CypHer or Alexa Fluor tags shows that preincubation with Aβ42 disrupts protein uptake. Our results identify a potential mechanism by which amyloidogenic aggregates impair cellular function through disruption of the endosomal-lysosomal pathway.
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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 Socratic graph.