ArticleProteomics2018
Quantitative Analysis of the Brain Ubiquitylome in Alzheimer's Disease.
Article in Proteomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Meta-analysis fails to show any correlation between protein abundance and ubiquitination changes.FEBS open bio · 2026Pooled it
- Ubiquitin signatures on aggregating proteins in neurodegeneration.Essays in biochemistry · 2025Review
- The deubiquitinase OTULIN regulates tau expression and RNA metabolism in neurons.Genomic psychiatry : advancing science from genes to society · 2025Article
- Deubiquitinating Enzymes Ubiquitin-Specific Proteases 7 and 10 Regulate TAU Aggregation.International journal of molecular sciences · 2025Article
- Making tau amyloid models in vitro: a crucial and underestimated challenge.FEBS letters · 2025Review
- Photocatalytic Diselenide Contraction as a Tool for Site-Selective Isosteric Ubiquitylation.Journal of peptide science : an official publication of the European Peptide Society · 2025Article
- Proteomic landscape of Alzheimer's disease: emerging technologies, advances and insights (2021 - 2025).Molecular neurodegeneration · 2025Review
- Cytoskeletal Proteins and Alzheimer's Disease Pathogenesis: Focusing on the Interplay with Tau Pathology.Biomolecules · 2025Review
- Diverse influences on tau aggregation and implications for disease progression.Genes & development · 2025Review
- Tau degradation in Alzheimer's disease: Mechanisms and therapeutic opportunities.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- The Mechanistic Link Between Tau-Driven Proteotoxic Stress and Cellular Senescence in Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Distinct regional vulnerability to Aβ and iron accumulation in post mortem AD brains.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Article
- Updates in Alzheimer's disease: from basic research to diagnosis and therapies.Translational neurodegeneration · 2024Review
- Post-translational modifications linked to preclinical Alzheimer's disease-related pathological and cognitive changes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Proteomic Signaling of Dual-Specificity Phosphatase 4 (DUSP4) in Alzheimer's Disease.Biomolecules · 2024Article
- Review
- Involvement of ubiquitination in Alzheimer's disease.Frontiers in neurology · 2024Review
- Detection, visualization and quantification of protein complexes in human Alzheimer's disease brains using proximity ligation assay.Scientific reports · 2023Article
- Specific post-translational modifications of soluble tau protein distinguishes Alzheimer's disease and primary tauopathies.Nature communications · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Several neurodegenerative diseases including Alzheimer's Disease (AD) are characterized by ubiquitin-positive pathological protein aggregates. Here, an immunoaffinity approach is utilized to enrich ubiquitylated isopeptides after trypsin digestion from five AD and five age-matched control postmortem brain tissues. Label-free MS-based proteomic analysis identifies 4291 unique ubiquitylation sites mapping to 1682 unique proteins. Differential enrichment analysis shows that over 800 ubiquitylation sites are significantly altered between AD and control cases. Of these, ≈80% are increased in AD, including seven poly ubiquitin linkages, which is consistent with proteolytic stress and high burden of ubiquitylated pathological aggregates in AD. The microtubule associated protein Tau, the core component of neurofibrillary tangles, has the highest number of increased sites of ubiquitylation per any protein in AD. Tau poly ubiquitylation from AD brain homogenates is confirmed by reciprocal co-immunoprecipitation and by affinity capture using tandem ubiquitin binding entities. Co-modified peptides, with both ubiquitylation and phosphorylation sites, are also enriched in AD. Notably, many of the co-modified peptides mapped to Tau within KXGS motifs in the microtubule binding region suggesting that crosstalk between phosphorylation and ubiquitylation occurs on Tau in AD. Overall, these findings highlight the utility of MS to map ubiquitylated substrates in human brain and provides insight into mechanisms underlying pathological protein posttranslational modification in AD.
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What OpenQuestion holds
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.