ArticleMolecular neurodegeneration2018
Structural and mechanistic aspects influencing the ADAM10-mediated shedding of the prion protein.
Article in Molecular neurodegeneration, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 56 citations in OpenAlex.
- Cellular prion protein and its derived peptides: multifaceted roles in neurodegenerative diseases and potential as biomarkers.Cell & bioscience · 2026Review
- Bovine Spongiform Encephalopathy: An Integrated Review of Prion Mechanisms, Neuroanatomy, and Control.Veterinary sciences · 2026Review
- ADAM10-Mediated Proteolytic Remodelling of Signalling and Adhesion Proteins on Brain Cell-Derived Small Extracellular Vesicles.Journal of extracellular biology · 2026Article
- D178N prion protein mutation endows RML prions with new strain properties that do not mimic human genetic prion diseases.Acta neuropathologica · 2026Article
- Two Sides of the Same Coin-Mechanistic Insight, Diagnostic Application and Therapeutic Translation of Bacterial and Host-Derived Extracellular Vesicles.Journal of extracellular biology · 2025Review
- Therapeutic Trajectories in Human Prion Diseases.Sub-cellular biochemistry · 2025Review
- Prion protein alters viral control and enhances pathology after perinatal cytomegalovirus infection.Nature communications · 2024Article
- Non-canonical function of ADAM10 in presynaptic plasticity.Cellular and molecular life sciences : CMLS · 2024Article
- Cleavage site-directed antibodies reveal the prion protein in humans is shed by ADAM10 at Y226 and associates with misfolded protein deposits in neurodegenerative diseases.Acta neuropathologica · 2024Article
- Differential expression of cellular prion protein (PrPJournal of neurovirology · 2024Article
- Inducing prion protein shedding as a neuroprotective and regenerative approach in pathological conditions of the brain: from theory to facts.Neural regeneration research · 2023Review
- Inhibition of DPAGT1 suppresses HER2 shedding and trastuzumab resistance in human breast cancer.The Journal of clinical investigation · 2023Article
- Diminished Neuronal ESCRT-0 Function Exacerbates AMPA Receptor Derangement and Accelerates Prion-Induced Neurodegeneration.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Anchorless risk or released benefit? An updated view on the ADAM10-mediated shedding of the prion protein.Cell and tissue research · 2023Review
- Proteolysis of CD44 at the cell surface controls a downstream protease network.Frontiers in molecular biosciences · 2023Article
- Human prion diseases and the prion protein - what is the current state of knowledge?Translational neuroscience · 2023Review
- Prion Protein: The Molecule of Many Forms and Faces.International journal of molecular sciences · 2022Review
- Ligands binding to the prion protein induce its proteolytic release with therapeutic potential in neurodegenerative proteinopathies.Science advances · 2021Article
- β-Cleavage of the prion protein in the human eye: Implications for the spread of infectious prions and human ocular disorders.Experimental eye research · 2021Article
- Cell Surface Processing of CD109 by Meprin β Leads to the Release of Soluble Fragments and Reduced Expression on Extracellular Vesicles.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
Abstract
Background: Proteolytic processing of the prion protein (PrP<superscript>C</superscript>) by endogenous proteases generates bioactive membrane-bound and soluble fragments which may help to explain the pleiotropic roles of this protein in the nervous system and in brain diseases. Shedding of almost full-length PrP<superscript>C</superscript> into the extracellular space by the metalloprotease ADAM10 is of peculiar relevance since soluble PrP stimulates axonal outgrowth and is protective in neurodegenerative conditions such as Alzheimer’s and prion disease. However, molecular determinates and mechanisms regulating the shedding of PrP are entirely unknown. Methods: We produced an antibody recognizing the neo-epitope of shed PrP generated by ADAM10 in biological samples and used it to study structural and mechanistic aspects affecting the shedding. For this, we investigated genetically modified cellular and murine models by biochemical and morphological approaches. Results: We show that the novel antibody specifically detects shed PrP in cell culture supernatants and murine brain. We demonstrate that ADAM10 is the exclusive sheddase of PrP<superscript>C</superscript> in the nervous system and reveal that the glycosylation state and type of membrane-anchorage of PrP<superscript>C</superscript> severely affect its shedding. Furthermore, we provide evidence that PrP shedding can be modulated by pharmacological inhibition and stimulation and present data suggesting that shedding is a relevant part of a compensatory network ensuring PrP<superscript>C</superscript> homeostasis of the cell. Conclusions: With the new antibody, our study introduces a new tool to reliably investigate PrP-shedding. In addition, this study provides novel and important insight into the regulation of this cleavage event, which is likely to be relevant for diagnostic and therapeutic approaches even beyond neurodegeneration.
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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.