IndraLab

Statements

USP14 inhibits MAPT. 6 / 6
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"The DUB USP14 suppresses turnover of Tau and TDP-43 in mouse embryonic fibroblasts (MEFs) by impairing the protea-some; therefore, small-molecule inhibitors of USP14 could help clear these toxic proteins from cells."
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"Previous in vitro studies indicated that either loss of USP14 or inhibition of USP14’s catalytic activity increased the degradation of both model proteasome substrates and over-expressed TARDBP, PRNP, and MAPT proteins in cultured cells (Hanna et al., 2006; Homma et al., 2015; Lee et al., 2010; Lee et al., 2011)."
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"A variant of IU1, called IU1-47, which was 10-fold more potent in inhibiting USP14’s ubiquitin hydrolase activity, also enhanced degradation of MAPT in primary cortical neurons (Boselli et al., 2017)."
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"Moreover, IU1-47, a small molecule inhibitor of USP14, was also shown to accelerate the degradation of tau protein (Table 2) (Boselli et al., 2017)."
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"USP14 aptamers enhanced tau degradation in cultured cells and protected against oxidative stress."
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"In conclusion, pharmacologically inhibiting (with low or high IU1 concentrations) or genetically down-regulating USP14 fail to enhance proteasomal degradation of Ub-proteins or Tau in neurons."
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