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• W2118611462 endingPage "2009" @default.
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• W2118611462 abstract "Loss-of-function diseases are often caused by destabilizing mutations that lead to protein misfolding and degradation. Modulating the innate protein homeostasis (proteostasis) capacity may lead to rescue of native folding of the mutated variants, thereby ameliorating the disease phenotype. In lysosomal storage disorders (LSDs), a number of highly prevalent alleles have missense mutations that do not impair the enzyme's catalytic activity but destabilize its native structure, resulting in the degradation of the misfolded protein. Enhancing the cellular folding capacity enables rescuing the native, biologically functional structure of these unstable mutated enzymes. However, proteostasis modulators specific for the lysosomal system are currently unknown. Here, we investigate the role of the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and function, in modulating lysosomal proteostasis in LSDs. We show that TFEB activation results in enhanced folding, trafficking and lysosomal activity of a severely destabilized glucocerebrosidase (GC) variant associated with the development of Gaucher disease (GD), the most common LSD. TFEB specifically induces the expression of GC and of key genes involved in folding and lysosomal trafficking, thereby enhancing both the pool of mutated enzyme and its processing through the secretory pathway. TFEB activation also rescues the activity of a β-hexosaminidase mutant associated with the development of another LSD, Tay–Sachs disease, thus suggesting general applicability of TFEB-mediated proteostasis modulation to rescue destabilizing mutations in LSDs. In summary, our findings identify TFEB as a specific regulator of lysosomal proteostasis and suggest that TFEB may be used as a therapeutic target to rescue enzyme homeostasis in LSDs." @default.
• W2118611462 created "2016-06-24" @default.
• W2118611462 creator A5008210618 @default.
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• W2118611462 date "2013-02-07" @default.
• W2118611462 modified "2023-10-16" @default.
• W2118611462 title "TFEB regulates lysosomal proteostasis" @default.
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• W2118611462 cites W1525577371 @default.
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• W2118611462 cites W1758125525 @default.
• W2118611462 cites W1965714350 @default.
• W2118611462 cites W1967331757 @default.
• W2118611462 cites W1968324562 @default.
• W2118611462 cites W1971510584 @default.
• W2118611462 cites W1972277010 @default.
• W2118611462 cites W1975200363 @default.
• W2118611462 cites W1975405079 @default.
• W2118611462 cites W1979904354 @default.
• W2118611462 cites W1987787530 @default.
• W2118611462 cites W1988396936 @default.
• W2118611462 cites W1988511393 @default.
• W2118611462 cites W1989746014 @default.
• W2118611462 cites W1995688301 @default.
• W2118611462 cites W2007348345 @default.
• W2118611462 cites W2008762154 @default.
• W2118611462 cites W2009975411 @default.
• W2118611462 cites W2020353337 @default.
• W2118611462 cites W2024747540 @default.
• W2118611462 cites W2024990739 @default.
• W2118611462 cites W2025837524 @default.
• W2118611462 cites W2026584056 @default.
• W2118611462 cites W2034118054 @default.
• W2118611462 cites W2034853531 @default.
• W2118611462 cites W2038961641 @default.
• W2118611462 cites W2040407461 @default.
• W2118611462 cites W2047059010 @default.
• W2118611462 cites W2048168961 @default.
• W2118611462 cites W2051526728 @default.
• W2118611462 cites W2057261483 @default.
• W2118611462 cites W2057347813 @default.
• W2118611462 cites W2058818863 @default.
• W2118611462 cites W2060496255 @default.
• W2118611462 cites W2061325032 @default.
• W2118611462 cites W2064599119 @default.
• W2118611462 cites W2071562149 @default.
• W2118611462 cites W2073592988 @default.
• W2118611462 cites W2076107153 @default.
• W2118611462 cites W2076159058 @default.
• W2118611462 cites W2077499130 @default.
• W2118611462 cites W2079133058 @default.
• W2118611462 cites W2091234795 @default.
• W2118611462 cites W2092011356 @default.
• W2118611462 cites W2093722439 @default.
• W2118611462 cites W2095706874 @default.
• W2118611462 cites W2099293163 @default.
• W2118611462 cites W2106771547 @default.
• W2118611462 cites W2107249189 @default.
• W2118611462 cites W2110436540 @default.
• W2118611462 cites W2114022615 @default.
• W2118611462 cites W2116505693 @default.
• W2118611462 cites W2117004136 @default.
• W2118611462 cites W2117073296 @default.
• W2118611462 cites W2118187647 @default.
• W2118611462 cites W2126489732 @default.
• W2118611462 cites W2130392121 @default.
• W2118611462 cites W2130410032 @default.
• W2118611462 cites W2144116764 @default.
• W2118611462 cites W2145822917 @default.
• W2118611462 cites W2147798737 @default.
• W2118611462 cites W2148659064 @default.
• W2118611462 cites W2153728088 @default.
• W2118611462 cites W2153824991 @default.
• W2118611462 cites W2156576736 @default.
• W2118611462 cites W2158217645 @default.
• W2118611462 cites W2163130181 @default.
• W2118611462 cites W2326372022 @default.
• W2118611462 cites W241406582 @default.
• W2118611462 cites W4234505218 @default.
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• W2118611462 doi "https://doi.org/10.1093/hmg/ddt052" @default.
• W2118611462 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23393155" @default.
• W2118611462 hasPublicationYear "2013" @default.
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