Matches in SemOpenAlex for { <https://semopenalex.org/work/W4362521569> ?p ?o ?g. }
- W4362521569 abstract "Current therapies for Fabry disease are based on reversing intracellular accumulation of globotriaosylceramide (Gb3) by enzyme replacement therapy (ERT) or chaperone-mediated stabilization of the defective enzyme, thereby alleviating lysosomal dysfunction. However, their effect in the reversal of end-organ damage, like kidney injury and chronic kidney disease, remains unclear. In this study, ultrastructural analysis of serial human kidney biopsies showed that long-term use of ERT reduced Gb3 accumulation in podocytes but did not reverse podocyte injury. Then, a CRISPR/Cas9-mediated α-galactosidase knockout podocyte cell line confirmed ERT-mediated reversal of Gb3 accumulation without resolution of lysosomal dysfunction. Transcriptome-based connectivity mapping and SILAC-based quantitative proteomics identified α-synuclein (SNCA) accumulation as a key event mediating podocyte injury. Genetic and pharmacological inhibition of SNCA improved lysosomal structure and function in Fabry podocytes, exceeding the benefits of ERT. Together, this work reconceptualizes Fabry-associated cell injury beyond Gb3 accumulation, and introduces SNCA modulation as a potential intervention, especially for patients with Fabry nephropathy." @default.
- W4362521569 created "2023-04-06" @default.
- W4362521569 creator A5000470800 @default.
- W4362521569 creator A5000783448 @default.
- W4362521569 creator A5001224102 @default.
- W4362521569 creator A5001829252 @default.
- W4362521569 creator A5004648123 @default.
- W4362521569 creator A5006394218 @default.
- W4362521569 creator A5006650621 @default.
- W4362521569 creator A5007623557 @default.
- W4362521569 creator A5015226386 @default.
- W4362521569 creator A5015296039 @default.
- W4362521569 creator A5016869649 @default.
- W4362521569 creator A5021849794 @default.
- W4362521569 creator A5023325095 @default.
- W4362521569 creator A5024283055 @default.
- W4362521569 creator A5026954074 @default.
- W4362521569 creator A5027240387 @default.
- W4362521569 creator A5031773278 @default.
- W4362521569 creator A5032811847 @default.
- W4362521569 creator A5041318104 @default.
- W4362521569 creator A5041922088 @default.
- W4362521569 creator A5042034514 @default.
- W4362521569 creator A5044946054 @default.
- W4362521569 creator A5045615753 @default.
- W4362521569 creator A5053495081 @default.
- W4362521569 creator A5054028455 @default.
- W4362521569 creator A5057863019 @default.
- W4362521569 creator A5058489462 @default.
- W4362521569 creator A5068133416 @default.
- W4362521569 creator A5068420758 @default.
- W4362521569 creator A5074405929 @default.
- W4362521569 creator A5075618597 @default.
- W4362521569 creator A5076632645 @default.
- W4362521569 creator A5077517489 @default.
- W4362521569 creator A5082171498 @default.
- W4362521569 creator A5083991053 @default.
- W4362521569 creator A5084594248 @default.
- W4362521569 creator A5085254910 @default.
- W4362521569 creator A5085653275 @default.
- W4362521569 date "2023-06-01" @default.
- W4362521569 modified "2023-10-04" @default.
- W4362521569 title "Accumulation of α-synuclein mediates podocyte injury in Fabry nephropathy" @default.
- W4362521569 cites W1529235958 @default.
- W4362521569 cites W1597336200 @default.
- W4362521569 cites W1898679873 @default.
- W4362521569 cites W1907174433 @default.
- W4362521569 cites W1961262965 @default.
- W4362521569 cites W1972774086 @default.
- W4362521569 cites W1974723464 @default.
- W4362521569 cites W1977709885 @default.
- W4362521569 cites W1998399313 @default.
- W4362521569 cites W1999359686 @default.
- W4362521569 cites W2004083498 @default.
- W4362521569 cites W2011480379 @default.
- W4362521569 cites W2015981234 @default.
- W4362521569 cites W2020681444 @default.
- W4362521569 cites W2022356406 @default.
- W4362521569 cites W2022649483 @default.
- W4362521569 cites W2026175550 @default.
- W4362521569 cites W2031601225 @default.
- W4362521569 cites W2040721946 @default.
- W4362521569 cites W2045435533 @default.
- W4362521569 cites W2049613365 @default.
- W4362521569 cites W2051719011 @default.
- W4362521569 cites W2055136539 @default.
- W4362521569 cites W2066304458 @default.
- W4362521569 cites W2069816309 @default.
- W4362521569 cites W2076388898 @default.
- W4362521569 cites W2084910880 @default.
- W4362521569 cites W2086197089 @default.
- W4362521569 cites W2089095199 @default.
- W4362521569 cites W2091164561 @default.
- W4362521569 cites W2091728196 @default.
- W4362521569 cites W2092976540 @default.
- W4362521569 cites W2098947710 @default.
- W4362521569 cites W2100884115 @default.
- W4362521569 cites W2110553827 @default.
- W4362521569 cites W2113915213 @default.
- W4362521569 cites W2119382610 @default.
- W4362521569 cites W2124364796 @default.
- W4362521569 cites W2128366873 @default.
- W4362521569 cites W2128801503 @default.
- W4362521569 cites W2129500342 @default.
- W4362521569 cites W2133118299 @default.
- W4362521569 cites W2133444266 @default.
- W4362521569 cites W2134451042 @default.
- W4362521569 cites W2146941726 @default.
- W4362521569 cites W2151748014 @default.
- W4362521569 cites W2152311269 @default.
- W4362521569 cites W2154717765 @default.
- W4362521569 cites W2165008949 @default.
- W4362521569 cites W2168432448 @default.
- W4362521569 cites W2168450345 @default.
- W4362521569 cites W2183562681 @default.
- W4362521569 cites W2234334991 @default.
- W4362521569 cites W2313827278 @default.
- W4362521569 cites W2337055769 @default.
- W4362521569 cites W2408805966 @default.
- W4362521569 cites W2416740612 @default.