ArticleMolecular brain2016
Dementia-linked amyloidosis is associated with brain protein deamidation as revealed by proteomic profiling of human brain tissues.
Article in Molecular brain, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 39 citations in OpenAlex.
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- The multifaceted role of hair as a biospecimen: recent advances in precision medicine and forensic science.Experimental & molecular medicine · 2025Review
- Advances in the Study of Protein Deamidation: Unveiling Its Influence on Aging, Disease Progression, Forensics and Therapeutic Efficacy.Proteomes · 2025Review
- TDP-43 proteinopathy in ALS is triggered by loss of ASRGL1 and associated with HML-2 expression.Nature communications · 2024Article
- Translational bioinformatics and data science for biomarker discovery in mental health: an analytical review.Briefings in bioinformatics · 2024Review
- The cellular modifier MOAG-4/SERF drives amyloid formation through charge complementation.The EMBO journal · 2021Article
- Metabolomics Signatures of Aging: Recent Advances.Aging and disease · 2021Review
- Serum albumin cysteine trioxidation is a potential oxidative stress biomarker of type 2 diabetes mellitus.Scientific reports · 2020Observational
- Accurate Identification of Deamidation and Citrullination from Global Shotgun Proteomics Data Using a Dual-Search Delta Score Strategy.Journal of proteome research · 2020Article
- Hypoxia-Induced Degenerative Protein Modifications Associated with Aging and Age-Associated Disorders.Aging and disease · 2020Review
- Dynamic expression of tRNA-derived small RNAs define cellular states.EMBO reports · 2019Article
- Human amyloid-β enriched extracts: evaluation of in vitro and in vivo internalization and molecular characterization.Alzheimer's research & therapy · 2019Article
- Quantitative profiling brain proteomes revealed mitochondrial dysfunction in Alzheimer's disease.Molecular brain · 2019Article
- Studies on the Proteome of Human Hair - Identification of Histones and Deamidated Keratins.Scientific reports · 2018Article
- Brain ureido degenerative protein modifications are associated with neuroinflammation and proteinopathy in Alzheimer's disease with cerebrovascular disease.Journal of neuroinflammation · 2017Article
- Increasing the accuracy of proteomic typing by decellularisation of amyloid tissue biopsies.Journal of proteomics · 2017Article
- LERLIC-MS/MS for In-depth Characterization and Quantification of Glutamine and Asparagine Deamidation in Shotgun Proteomics.Journal of visualized experiments : JoVE · 2017Article
- Future of the Genetic Code.Life (Basel, Switzerland) · 2017Review
- Insight of brain degenerative protein modifications in the pathology of neurodegeneration and dementia by proteomic profiling.Molecular brain · 2016Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAggregation of malformed proteins is a key feature of many neurodegenerative diseases, but the mechanisms that drive proteinopathy in the brain are poorly understood. We aimed to characterize aggregated proteins in human brain tissues affected by dementia.
resultsTo characterize amyloidal plaque purified from post-mortem brain tissue of dementia patient, we applied ultracentrifugation-electrostatic repulsion hydrophilic interaction chromatography (UC-ERLIC) coupled mass spectrometry-based proteomics technologies. Proteomics profiling of both soluble and aggregated amyloidal plaque demonstrated significant enrichment and deamidation of S100A9, ferritin, hemoglobin subunits, creatine kinase and collagen protein among the aggregated brain proteins. Amyloidal plaques were enriched in the deamidated variant of protein S100A9, and structural analysis indicated that both the low- and high-affinity calcium binding motifs of S100A9 were deamidated exclusively in the aggregated fraction, suggesting altered charge state and function of this protein in brain tissues affected by dementia. The multiple deamidated residues of S100A9 predicts introduction of negative charge that alter Ca(++) binding, suggesting increased capacity to form pathological aggregates in the brain.
conclusionUC-coupled proteomics revealed that brain amyloidal plaques are enriched in deamidated proteins, and suggested that altered charge state and calcium-binding capacity of S100A9 may enhance protein aggregation and promote neurodegeneration in the human brain.
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