FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2897097320> ?p ?o ?g. }

• W2897097320 abstract "Alzheimer's disease (AD) is characterized by the deposition of protein aggregates such as neurofibrillary tangles (NFTs) and amyloid (Aβ) plaques in the brain. Post-translational modification through ubiquitylation plays critical roles in clearing misfolded protein aggregates. Global changes in brain ubiquitylation patterns on tau and other proteins in AD brain is lacking. Investigating global ubiquitylation changes in AD brain may provide insights regarding the underlying mechanisms of proteostasis, disease pathogenesis and potentially the identification of novel diagnostic biomarkers. An immunoaffinity approach was used to specifically enrich ubiquitinated (di-glycine) peptides from postmortem human control and AD brain tissues followed by liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) for identification and quantification of global ubiquitination sites associated with AD pathology. LC-MS/MS analysis identified 4,311 ubiquitin peptides mapping to 1,504 unique protein groups. Differential enrichment analysis showed 834 ubiquitylation sites were significantly altered between AD and control brain samples with at least 1.5-fold change. Eighty percent of these ubiquitin sites were enriched, whereas 20 percent were decreased in AD compared to controls. Hierarchical clustering of the human brain ubiquitylome clearly classified AD cases from healthy controls based on ubiquitylation patterns. Polyubiquitin linkage analysis identified increased levels of all seven polyubiquitin linkage types as well as total ubiquitin in the AD brain tissues. We report identification of 28 tau ubiquitylation sites from human brain samples, of which 15 are novel. These sites occur within proline-rich and microtubule binding repeat of tau with potential implications for tau protein interaction and aggregation. Doubly modified peptides with both phosphorylation and ubiquitylation, many of which originated from tau protein are differentially enriched in AD. Furthermore, all the KXGS motifs within the microtubule binding region (MTBR) of tau protein which represents the core of NFTs are enriched among doubly modified peptides. Collectively, these studies highlight the utility of an immunoaffinity enrichment approach coupled with MS analysis to mapping AD associated global ubiquitylome changes as well as gaining insights into underlying proteostasis pathways altered in AD and potential identification of novel diagnostic biomarkers." @default.
• W2897097320 created "2018-10-26" @default.
• W2897097320 creator A5022349887 @default.
• W2897097320 creator A5023920651 @default.
• W2897097320 creator A5054941736 @default.
• W2897097320 creator A5061526409 @default.
• W2897097320 creator A5063226548 @default.
• W2897097320 creator A5075380727 @default.
• W2897097320 creator A5080612573 @default.
• W2897097320 date "2018-07-01" @default.
• W2897097320 modified "2023-10-16" @default.
• W2897097320 title "P3‐191: COMPREHENSIVE MAPPING OF ALZHEIMER'S DISEASE BRAIN UBIQUITYLOME" @default.
• W2897097320 doi "https://doi.org/10.1016/j.jalz.2018.06.1549" @default.
• W2897097320 hasPublicationYear "2018" @default.
• W2897097320 type Work @default.
• W2897097320 sameAs 2897097320 @default.
• W2897097320 citedByCount "0" @default.
• W2897097320 crossrefType "journal-article" @default.
• W2897097320 hasAuthorship W2897097320A5022349887 @default.
• W2897097320 hasAuthorship W2897097320A5023920651 @default.
• W2897097320 hasAuthorship W2897097320A5054941736 @default.
• W2897097320 hasAuthorship W2897097320A5061526409 @default.
• W2897097320 hasAuthorship W2897097320A5063226548 @default.
• W2897097320 hasAuthorship W2897097320A5075380727 @default.
• W2897097320 hasAuthorship W2897097320A5080612573 @default.
• W2897097320 hasConcept C104317684 @default.
• W2897097320 hasConcept C169760540 @default.
• W2897097320 hasConcept C185592680 @default.
• W2897097320 hasConcept C203014093 @default.
• W2897097320 hasConcept C25602115 @default.
• W2897097320 hasConcept C2777670902 @default.
• W2897097320 hasConcept C2780942790 @default.
• W2897097320 hasConcept C2781452922 @default.
• W2897097320 hasConcept C55493867 @default.
• W2897097320 hasConcept C86803240 @default.
• W2897097320 hasConceptScore W2897097320C104317684 @default.
• W2897097320 hasConceptScore W2897097320C169760540 @default.
• W2897097320 hasConceptScore W2897097320C185592680 @default.
• W2897097320 hasConceptScore W2897097320C203014093 @default.
• W2897097320 hasConceptScore W2897097320C25602115 @default.
• W2897097320 hasConceptScore W2897097320C2777670902 @default.
• W2897097320 hasConceptScore W2897097320C2780942790 @default.
• W2897097320 hasConceptScore W2897097320C2781452922 @default.
• W2897097320 hasConceptScore W2897097320C55493867 @default.
• W2897097320 hasConceptScore W2897097320C86803240 @default.
• W2897097320 hasIssue "7S_Part_21" @default.
• W2897097320 hasLocation W28970973201 @default.
• W2897097320 hasOpenAccess W2897097320 @default.
• W2897097320 hasPrimaryLocation W28970973201 @default.
• W2897097320 hasRelatedWork W1583996972 @default.
• W2897097320 hasRelatedWork W2054348461 @default.
• W2897097320 hasRelatedWork W2067813647 @default.
• W2897097320 hasRelatedWork W2462325035 @default.
• W2897097320 hasRelatedWork W2531635260 @default.
• W2897097320 hasRelatedWork W2756550877 @default.
• W2897097320 hasRelatedWork W2802845690 @default.
• W2897097320 hasRelatedWork W2809090369 @default.
• W2897097320 hasRelatedWork W2944740206 @default.
• W2897097320 hasRelatedWork W3134538560 @default.
• W2897097320 hasVolume "14" @default.
• W2897097320 isParatext "false" @default.
• W2897097320 isRetracted "false" @default.
• W2897097320 magId "2897097320" @default.
• W2897097320 workType "article" @default.