FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2045831415> ?p ?o ?g. }

• W2045831415 endingPage "28397" @default.
• W2045831415 startingPage "28386" @default.
• W2045831415 abstract "Fabry disease is a lysosomal storage disorder caused by loss of α-galactosidase function. More than 500 Fabry disease mutants have been identified, the majority of which are structurally destabilized. A therapeutic strategy under development for lysosomal storage diseases consists of using pharmacological chaperones to stabilize the structure of the mutant protein, thereby promoting lysosomal delivery over retrograde degradation. The substrate analog 1-deoxygalactonojirimycin (DGJ) has been shown to restore activity of mutant α-galactosidase and is currently in clinical trial for treatment of Fabry disease. However, only ∼65% of tested mutants respond to treatment in cultured patient fibroblasts, and the structural underpinnings of DGJ response remain poorly explained. Using computational modeling and cell culture experiments, we show that the DGJ response is negatively affected by protein aggregation of α-galactosidase mutants, revealing a qualitative difference between misfolding-associated and aggregation-associated loss of function. A scoring function combining predicted thermodynamic stability and intrinsic aggregation propensity of mutants captures well their aggregation behavior under overexpression in HeLa cells. Interestingly, the same classifier performs well on DGJ response data of patient-derived cultured lymphoblasts, showing that protein aggregation is an important determinant of chemical chaperone efficiency under endogenous expression levels as well. Our observations reinforce the idea that treatment of aggregation-associated loss of function observed for the more severe α-galactosidase mutants could be enhanced by combining pharmacological chaperone treatment with the suppression of mutant aggregation, e.g. via proteostatic regulator compounds that increase cellular chaperone expression." @default.
• W2045831415 created "2016-06-24" @default.
• W2045831415 creator A5008256216 @default.
• W2045831415 creator A5018247276 @default.
• W2045831415 creator A5031589452 @default.
• W2045831415 creator A5039155418 @default.
• W2045831415 creator A5039735549 @default.
• W2045831415 creator A5063121400 @default.
• W2045831415 creator A5068993139 @default.
• W2045831415 creator A5069362675 @default.
• W2045831415 creator A5070924824 @default.
• W2045831415 creator A5080234805 @default.
• W2045831415 date "2012-08-01" @default.
• W2045831415 modified "2023-10-02" @default.
• W2045831415 title "α-Galactosidase Aggregation Is a Determinant of Pharmacological Chaperone Efficacy on Fabry Disease Mutants" @default.
• W2045831415 cites W1530374442 @default.
• W2045831415 cites W1568892768 @default.
• W2045831415 cites W1597854169 @default.
• W2045831415 cites W1975365119 @default.
• W2045831415 cites W1982057831 @default.
• W2045831415 cites W1985267699 @default.
• W2045831415 cites W1988050069 @default.
• W2045831415 cites W1991214026 @default.
• W2045831415 cites W1991968375 @default.
• W2045831415 cites W1997441065 @default.
• W2045831415 cites W2006892813 @default.
• W2045831415 cites W2010687395 @default.
• W2045831415 cites W2014297210 @default.
• W2045831415 cites W2017846028 @default.
• W2045831415 cites W2022356406 @default.
• W2045831415 cites W2023490488 @default.
• W2045831415 cites W2026507072 @default.
• W2045831415 cites W2026552146 @default.
• W2045831415 cites W2027249807 @default.
• W2045831415 cites W2027839322 @default.
• W2045831415 cites W2031311803 @default.
• W2045831415 cites W2039775392 @default.
• W2045831415 cites W2040321992 @default.
• W2045831415 cites W2040721946 @default.
• W2045831415 cites W2040965053 @default.
• W2045831415 cites W2043774580 @default.
• W2045831415 cites W2045282740 @default.
• W2045831415 cites W2058754026 @default.
• W2045831415 cites W2059428912 @default.
• W2045831415 cites W2067328535 @default.
• W2045831415 cites W2067620347 @default.
• W2045831415 cites W2078005095 @default.
• W2045831415 cites W2092011356 @default.
• W2045831415 cites W2092976540 @default.
• W2045831415 cites W2099099776 @default.
• W2045831415 cites W2101225287 @default.
• W2045831415 cites W2116313758 @default.
• W2045831415 cites W2119711780 @default.
• W2045831415 cites W2141104259 @default.
• W2045831415 cites W2147001430 @default.
• W2045831415 cites W2149659010 @default.
• W2045831415 cites W2156576736 @default.
• W2045831415 cites W2168879855 @default.
• W2045831415 cites W2169237458 @default.
• W2045831415 cites W4211088838 @default.
• W2045831415 doi "https://doi.org/10.1074/jbc.m112.351056" @default.
• W2045831415 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3436532" @default.
• W2045831415 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22773828" @default.
• W2045831415 hasPublicationYear "2012" @default.
• W2045831415 type Work @default.
• W2045831415 sameAs 2045831415 @default.
• W2045831415 citedByCount "31" @default.
• W2045831415 countsByYear W20458314152013 @default.
• W2045831415 countsByYear W20458314152014 @default.
• W2045831415 countsByYear W20458314152015 @default.
• W2045831415 countsByYear W20458314152016 @default.
• W2045831415 countsByYear W20458314152017 @default.
• W2045831415 countsByYear W20458314152018 @default.
• W2045831415 countsByYear W20458314152019 @default.
• W2045831415 countsByYear W20458314152020 @default.
• W2045831415 countsByYear W20458314152022 @default.
• W2045831415 countsByYear W20458314152023 @default.
• W2045831415 crossrefType "journal-article" @default.
• W2045831415 hasAuthorship W2045831415A5008256216 @default.
• W2045831415 hasAuthorship W2045831415A5018247276 @default.
• W2045831415 hasAuthorship W2045831415A5031589452 @default.
• W2045831415 hasAuthorship W2045831415A5039155418 @default.
• W2045831415 hasAuthorship W2045831415A5039735549 @default.
• W2045831415 hasAuthorship W2045831415A5063121400 @default.
• W2045831415 hasAuthorship W2045831415A5068993139 @default.
• W2045831415 hasAuthorship W2045831415A5069362675 @default.
• W2045831415 hasAuthorship W2045831415A5070924824 @default.
• W2045831415 hasAuthorship W2045831415A5080234805 @default.
• W2045831415 hasBestOaLocation W20458314151 @default.
• W2045831415 hasConcept C104317684 @default.
• W2045831415 hasConcept C127716648 @default.
• W2045831415 hasConcept C136238340 @default.
• W2045831415 hasConcept C142724271 @default.
• W2045831415 hasConcept C143065580 @default.
• W2045831415 hasConcept C185592680 @default.
• W2045831415 hasConcept C204328495 @default.
• W2045831415 hasConcept C2775962898 @default.
• W2045831415 hasConcept C2777404818 @default.

• next