FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2014536738> ?p ?o ?g. }

• W2014536738 endingPage "48" @default.
• W2014536738 startingPage "35" @default.
• W2014536738 abstract "Age-dependent neurodegenerative diseases progressively form aggregates containing both shared components (e.g., TDP-43, phosphorylated tau) and proteins specific to each disease. We investigated whether diverse neuropathies might have additional aggregation-prone proteins in common, discoverable by proteomics. Caenorhabditis elegans expressing unc-54p/Q40::YFP, a model of polyglutamine array diseases such as Huntington's, accrues aggregates in muscle 2-6 days posthatch. These foci, isolated on antibody-coupled magnetic beads, were characterized by high-resolution mass spectrometry. Three Q40::YFP-associated proteins were inferred to promote aggregation and cytotoxicity, traits reduced or delayed by their RNA interference knockdown. These RNAi treatments also retarded aggregation/cytotoxicity in Alzheimer's disease models, nematodes with muscle or pan-neuronal Aβ₁₋₄₂ expression and behavioral phenotypes. The most abundant aggregated proteins are glutamine/asparagine-rich, favoring hydrophobic interactions with other random-coil domains. A particularly potent modulator of aggregation, CRAM-1/HYPK, contributed < 1% of protein aggregate peptides, yet its knockdown reduced Q40::YFP aggregates 72-86% (P < 10(-6) ). In worms expressing Aβ₁₋₄₂, knockdown of cram-1 reduced β-amyloid 60% (P < 0.002) and slowed age-dependent paralysis > 30% (P < 10(-6)). In wild-type worms, cram-1 knockdown reduced aggregation and extended lifespan, but impaired early reproduction. Protection against seeded aggregates requires proteasome function, implying that normal CRAM-1 levels promote aggregation by interfering with proteasomal degradation of misfolded proteins. Molecular dynamic modeling predicts spontaneous and stable interactions of CRAM-1 (or human orthologs) with ubiquitin, and we verified that CRAM-1 reduces degradation of a tagged-ubiquitin reporter. We propose that CRAM-1 exemplifies a class of primitive chaperones that are initially protective and highly beneficial for early reproduction, but ultimately impair aggregate clearance and limit longevity." @default.
• W2014536738 created "2016-06-24" @default.
• W2014536738 creator A5027424927 @default.
• W2014536738 creator A5039791222 @default.
• W2014536738 creator A5060384504 @default.
• W2014536738 creator A5062144523 @default.
• W2014536738 creator A5080232976 @default.
• W2014536738 creator A5085718214 @default.
• W2014536738 date "2014-12-16" @default.
• W2014536738 modified "2023-10-17" @default.
• W2014536738 title "Proteins in aggregates functionally impact multiple neurodegenerative disease models by forming proteasome‐blocking complexes" @default.
• W2014536738 cites W1488807150 @default.
• W2014536738 cites W1910955584 @default.
• W2014536738 cites W1947804549 @default.
• W2014536738 cites W1963579854 @default.
• W2014536738 cites W1970888117 @default.
• W2014536738 cites W1975769486 @default.
• W2014536738 cites W1980947093 @default.
• W2014536738 cites W1981247519 @default.
• W2014536738 cites W1985567442 @default.
• W2014536738 cites W1987820478 @default.
• W2014536738 cites W1987879799 @default.
• W2014536738 cites W1989235034 @default.
• W2014536738 cites W1995306841 @default.
• W2014536738 cites W1996054899 @default.
• W2014536738 cites W1998937554 @default.
• W2014536738 cites W2003614590 @default.
• W2014536738 cites W2004178008 @default.
• W2014536738 cites W2015978979 @default.
• W2014536738 cites W2017587511 @default.
• W2014536738 cites W2022532556 @default.
• W2014536738 cites W2027901215 @default.
• W2014536738 cites W2032730097 @default.
• W2014536738 cites W2045848640 @default.
• W2014536738 cites W2047205406 @default.
• W2014536738 cites W2055807633 @default.
• W2014536738 cites W2067297186 @default.
• W2014536738 cites W2067680463 @default.
• W2014536738 cites W2068275936 @default.
• W2014536738 cites W2074759905 @default.
• W2014536738 cites W2082429191 @default.
• W2014536738 cites W2084406437 @default.
• W2014536738 cites W2084415184 @default.
• W2014536738 cites W2089109086 @default.
• W2014536738 cites W2089145020 @default.
• W2014536738 cites W2095785516 @default.
• W2014536738 cites W2112928083 @default.
• W2014536738 cites W2120722343 @default.
• W2014536738 cites W2121074963 @default.
• W2014536738 cites W2123625999 @default.
• W2014536738 cites W2128679613 @default.
• W2014536738 cites W2136062554 @default.
• W2014536738 cites W2144713781 @default.
• W2014536738 cites W2148581106 @default.
• W2014536738 cites W2152217159 @default.
• W2014536738 cites W2156168338 @default.
• W2014536738 cites W2157961462 @default.
• W2014536738 cites W2170111492 @default.
• W2014536738 doi "https://doi.org/10.1111/acel.12296" @default.
• W2014536738 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4326912" @default.
• W2014536738 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25510159" @default.
• W2014536738 hasPublicationYear "2014" @default.
• W2014536738 type Work @default.
• W2014536738 sameAs 2014536738 @default.
• W2014536738 citedByCount "50" @default.
• W2014536738 countsByYear W20145367382015 @default.
• W2014536738 countsByYear W20145367382016 @default.
• W2014536738 countsByYear W20145367382017 @default.
• W2014536738 countsByYear W20145367382018 @default.
• W2014536738 countsByYear W20145367382019 @default.
• W2014536738 countsByYear W20145367382020 @default.
• W2014536738 countsByYear W20145367382021 @default.
• W2014536738 countsByYear W20145367382022 @default.
• W2014536738 countsByYear W20145367382023 @default.
• W2014536738 crossrefType "journal-article" @default.
• W2014536738 hasAuthorship W2014536738A5027424927 @default.
• W2014536738 hasAuthorship W2014536738A5039791222 @default.
• W2014536738 hasAuthorship W2014536738A5060384504 @default.
• W2014536738 hasAuthorship W2014536738A5062144523 @default.
• W2014536738 hasAuthorship W2014536738A5080232976 @default.
• W2014536738 hasAuthorship W2014536738A5085718214 @default.
• W2014536738 hasBestOaLocation W20145367381 @default.
• W2014536738 hasConcept C104292427 @default.
• W2014536738 hasConcept C104317684 @default.
• W2014536738 hasConcept C136238340 @default.
• W2014536738 hasConcept C166703698 @default.
• W2014536738 hasConcept C173396325 @default.
• W2014536738 hasConcept C190283241 @default.
• W2014536738 hasConcept C27740335 @default.
• W2014536738 hasConcept C2777633098 @default.
• W2014536738 hasConcept C2778944004 @default.
• W2014536738 hasConcept C2781452922 @default.
• W2014536738 hasConcept C2992195973 @default.
• W2014536738 hasConcept C55493867 @default.
• W2014536738 hasConcept C59822182 @default.
• W2014536738 hasConcept C67705224 @default.
• W2014536738 hasConcept C86803240 @default.
• W2014536738 hasConcept C95444343 @default.

• next