ArticleThe Journal of biological chemistry2012
Phosphorylation of amyloid-β peptide at serine 8 attenuates its clearance via insulin-degrading and angiotensin-converting enzymes.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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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
40 citing papers in PubMed, 80 citations in OpenAlex.
- Protein Modifications and Quality Control System: Target for Alzheimer's Disease Therapy.International journal of molecular sciences · 2026Review
- Amyloid Beta in Alzheimer's Disease: Mechanisms, Biomarker Potential, and Therapeutic Targets.CNS neuroscience & therapeutics · 2025Review
- Aggregation-Dependent Epitope Sequence and Modification Fingerprints of Anti-Aβ Antibodies.bioRxiv : the preprint server for biology · 2025Article
- Bifurcations in coupled amyloid-β aggregation-inflammation systems.NPJ systems biology and applications · 2024Article
- Phosphorylation-state dependent intraneuronal sorting of Aβ differentially impairs autophagy and the endo-lysosomal system.Autophagy · 2024Article
- Amyloid fibril proteomics of AD brains reveals modifiers of aggregation and toxicity.Molecular neurodegeneration · 2023Article
- Structural polymorphism and cytotoxicity of brain-derived β-amyloid extracts.Protein science : a publication of the Protein Society · 2023Review
- Review
- Comparative Hydrophobic Core Dynamics Between Wild-Type Amyloid-β Fibrils, Glutamate-3 Truncation, and Serine-8 Phosphorylation.Chemphyschem : a European journal of chemical physics and physical chemistry · 2022Article
- Article
- TREM2 modulates differential deposition of modified and non-modified Aβ species in extracellular plaques and intraneuronal deposits.Acta neuropathologica communications · 2021Article
- Consequences of post-translational modifications on amyloid proteins as revealed by protein semisynthesis.Current opinion in chemical biology · 2021Review
- Proteolytic α-Synuclein Cleavage in Health and Disease.International journal of molecular sciences · 2021Review
- Racemization in Post-Translational Modifications Relevance to Protein Aging, Aggregation and Neurodegeneration: Tip of the Iceberg.Symmetry · 2021Article
- Phosphorylated Aβ peptides in human Down syndrome brain and different Alzheimer's-like mouse models.Acta neuropathologica communications · 2020Article
- Acetylation of Aβ42 at Lysine 16 Disrupts Amyloid Formation.ACS chemical neuroscience · 2020Article
- Chiral Interface of Amyloid Beta (Aβ): Relevance to Protein Aging, Aggregation and Neurodegeneration.Symmetry · 2020Article
- PI3K activation prevents Aβ42-induced synapse loss and favors insoluble amyloid deposit formation.Molecular biology of the cell · 2020Article
- Novel Phosphorylation-State Specific Antibodies Reveal Differential Deposition of Ser26 Phosphorylated Aβ Species in a Mouse Model of Alzheimer's Disease.Frontiers in molecular neuroscience · 2020Article
- Phosphorylation mapping of Laminin β1-chain: Kinases in association with active sites.Journal of biosciences · 2019Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulation of amyloid-β peptides (Aβ) in the brain is a common pathological feature of Alzheimer disease (AD). Aggregates of Aβ are neurotoxic and appear to be critically involved in the neurodegeneration during AD pathogenesis. Accumulation of Aβ could be caused by increased production, as indicated by several mutations in the amyloid precursor protein or the γ-secretase components presenilin-1 and presenilin-2 that cause familial early-onset AD. However, recent data also indicate a decreased clearance rate of Aβ in AD brains. We recently demonstrated that Aβ undergoes phosphorylation by extracellular or cell surface-localized protein kinase A, leading to increased aggregation. Here, we provide evidence that phosphorylation of monomeric Aβ at Ser-8 also decreases its clearance by microglial cells. By using mass spectrometry, we demonstrate that phosphorylation at Ser-8 inhibited the proteolytic degradation of monomeric Aβ by the insulin-degrading enzyme, a major Aβ-degrading enzyme released from microglial cells. Phosphorylation also decreased the degradation of Aβ by the angiotensin-converting enzyme. In contrast, Aβ degradation by plasmin was largely unaffected by phosphorylation. Thus, phosphorylation of Aβ could play a dual role in Aβ metabolism. It decreases its proteolytic clearance and also promotes its aggregation. The inhibition of extracellular Aβ phosphorylation, stimulation of protease expression and/or their proteolytic activity could be explored to promote Aβ degradation in AD therapy or prevention.
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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.