Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/82857
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dc.contributor.authorAdav, Sunil S.en
dc.contributor.authorGallart-Palau, Xavieren
dc.contributor.authorTan, Kok Hianen
dc.contributor.authorLim, Sai Kiangen
dc.contributor.authorTam, James Pingkwanen
dc.contributor.authorSze, Siu Kwanen
dc.date.accessioned2016-03-22T06:39:47Zen
dc.date.accessioned2019-12-06T15:06:59Z-
dc.date.available2016-03-22T06:39:47Zen
dc.date.available2019-12-06T15:06:59Z-
dc.date.issued2016en
dc.identifier.citationAdav, S. S., Gallart-Palau, X., Tan, K. H., Lim, S. K., Tam, J. P., & Sze, S. K. (2016). Dementia-linked amyloidosis is associated with brain protein deamidation as revealed by proteomic profiling of human brain tissues. Molecular Brain, 9, 20-.en
dc.identifier.issn1756-6606en
dc.identifier.urihttps://hdl.handle.net/10356/82857-
dc.identifier.urihttp://hdl.handle.net/10220/40312en
dc.description.abstractBackground: Aggregation 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. Results: To 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. Conclusion: UC-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.en
dc.description.sponsorshipNRF (Natl Research Foundation, S’pore)en
dc.description.sponsorshipMOE (Min. of Education, S’pore)en
dc.format.extent10 p.en
dc.language.isoenen
dc.relation.ispartofseriesMolecular Brainen
dc.rights© 2016 Adav et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en
dc.subjectNeurodegenerative diseaseen
dc.subjectAmyloidsen
dc.subjectMitochondrial creatine kinaseen
dc.subjectDeamidationen
dc.subjectBrain Proteomeen
dc.subjectProtein S100A9en
dc.titleDementia-linked amyloidosis is associated with brain protein deamidation as revealed by proteomic profiling of human brain tissuesen
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen
dc.identifier.doihttp://dx.doi.org/10.1186/s13041-016-0200-zen
dc.description.versionPublished versionen
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