ArticleProceedings of the National Academy of Sciences of the United States of America2007
Cellular prion protein regulates beta-secretase cleavage of the Alzheimer's amyloid precursor protein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers, 2 of them syntheses that pooled it.
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Who cites it
126 citing papers in PubMed, 2 syntheses or guidelines pooled it, 259 citations in OpenAlex.
- CT1812 biomarker signature from a meta-analysis of CSF proteomic findings from two Phase 2 clinical trials in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Pooled it
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- The Potential Regulators of Amyloidogenic Pathway of APP Processing in Alzheimer's Disease.Biomedicines · 2025Review
- The duality of amyloid-β: its role in normal and Alzheimer's disease states.Molecular brain · 2024Review
- Cellular prion protein offers neuroprotection in astrocytes submitted to amyloid β oligomer toxicity.Molecular and cellular biochemistry · 2023Article
- The Strategies of Development of New Non-Toxic Inhibitors of Amyloid Formation.International journal of molecular sciences · 2023Review
- Chemistry and Function of Glycosaminoglycans in the Nervous System.Advances in neurobiology · 2023Review
- A Function of Amyloid-β in Mediating Activity-Dependent Axon/Synapse Competition May Unify Its Roles in Brain Physiology and Pathology.Journal of Alzheimer's disease : JAD · 2023Review
- Sirt3 deficiency induced down regulation of insulin degrading enzyme in comorbid Alzheimer's disease with metabolic syndrome.Scientific reports · 2022Article
- Review
- APP deficiency and HTRA2 modulates PrPBBA advances · 2022Article
- Amyloid precursor protein (APP) and amyloid β (Aβ) interact with cell adhesion molecules: Implications in Alzheimer's disease and normal physiology.Frontiers in cell and developmental biology · 2022Review
- 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
- Distribution of microRNA profiles in pre-clinical and clinical forms of murine and human prion disease.Communications biology · 2021Article
- Extracellular Protein Aggregates Colocalization and Neuronal Dystrophy in Comorbid Alzheimer's and Creutzfeldt-Jakob Disease: A Micromorphological Pilot Study on 20 Brains.International journal of molecular sciences · 2021Article
- Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression.Frontiers in immunology · 2021Article
- Understanding Creutzfeldt-Jackob disease from a viewpoint of amyloidogenic evolvability.Prion · 2020Review
- Cellular Prion Protein (PrPc): Putative Interacting Partners and Consequences of the Interaction.International journal of molecular sciences · 2020Review
- N-Terminal Regions of Prion Protein: Functions and Roles in Prion Diseases.International journal of molecular sciences · 2020Review
- Review
66 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Proteolytic processing of the amyloid precursor protein (APP) by beta-secretase, beta-site APP cleaving enzyme (BACE1), is the initial step in the production of the amyloid beta (Abeta) peptide, which is involved in the pathogenesis of Alzheimer's disease. The normal cellular function of the prion protein (PrP(C)), the causative agent of the transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease in humans, remains enigmatic. Because both APP and PrP(C) are subject to proteolytic processing by the same zinc metalloproteases, we tested the involvement of PrP(C) in the proteolytic processing of APP. Cellular overexpression of PrP(C) inhibited the beta-secretase cleavage of APP and reduced Abeta formation. Conversely, depletion of PrP(C) in mouse N2a cells by siRNA led to an increase in Abeta peptides secreted into the medium. In the brains of PrP knockout mice and in the brains from two strains of scrapie-infected mice, Abeta levels were significantly increased. Two mutants of PrP, PG14 and A116V, that are associated with familial human prion diseases failed to inhibit the beta-secretase cleavage of APP. Using constructs of PrP, we show that this regulatory effect of PrP(C) on the beta-secretase cleavage of APP required the localization of PrP(C) to cholesterol-rich lipid rafts and was mediated by the N-terminal polybasic region of PrP(C) via interaction with glycosaminoglycans. In conclusion, this is a mechanism by which the cellular production of the neurotoxic Abeta is regulated by PrP(C) and may have implications for both Alzheimer's and prion diseases.
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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.