FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2070301080> ?p ?o ?g. }

• W2070301080 endingPage "12088" @default.
• W2070301080 startingPage "12079" @default.
• W2070301080 abstract "Alzheimer's disease and other tauopathies have recently been clustered with a group of nervous system disorders termed protein misfolding diseases. The common element established between these disorders is their requirement for processing by the chaperone complex. It is now clear that the individual components of the chaperone system, such as Hsp70 and Hsp90, exist in an intricate signaling network that exerts pleiotropic effects on a host of substrates. Therefore, we have endeavored to identify new compounds that can specifically regulate individual components of the chaperone family. Here, we hypothesized that chemical manipulation of Hsp70 ATPase activity, a target that has not previously been pursued, could illuminate a new pathway toward chaperone-based therapies. Using a newly developed high-throughput screening system, we identified inhibitors and activators of Hsp70 enzymatic activity. Inhibitors led to rapid proteasome-dependent tau degradation in a cell-based model. Conversely, Hsp70 activators preserved tau levels in the same system. Hsp70 inhibition did not result in general protein degradation, nor did it induce a heat shock response. We also found that inhibiting Hsp70 ATPase activity after increasing its expression levels facilitated tau degradation at lower doses, suggesting that we can combine genetic and pharmacologic manipulation of Hsp70 to control the fate of bound substrates. Disease relevance of this strategy was further established when tau levels were rapidly and substantially reduced in brain tissue from tau transgenic mice. These findings reveal an entirely novel path toward therapeutic intervention of tauopathies by inhibition of the previously untargeted ATPase activity of Hsp70." @default.
• W2070301080 created "2016-06-24" @default.
• W2070301080 creator A5008674482 @default.
• W2070301080 creator A5009411980 @default.
• W2070301080 creator A5018156812 @default.
• W2070301080 creator A5032532137 @default.
• W2070301080 creator A5045363726 @default.
• W2070301080 creator A5046928489 @default.
• W2070301080 creator A5052932581 @default.
• W2070301080 creator A5057034557 @default.
• W2070301080 creator A5060699815 @default.
• W2070301080 creator A5062473042 @default.
• W2070301080 creator A5063630066 @default.
• W2070301080 creator A5067529915 @default.
• W2070301080 creator A5071434472 @default.
• W2070301080 creator A5076967941 @default.
• W2070301080 creator A5084141510 @default.
• W2070301080 date "2009-09-30" @default.
• W2070301080 modified "2023-10-14" @default.
• W2070301080 title "Chemical Manipulation of Hsp70 ATPase Activity Regulates Tau Stability" @default.
• W2070301080 cites W1494494379 @default.
• W2070301080 cites W1514163719 @default.
• W2070301080 cites W1538781188 @default.
• W2070301080 cites W1583428545 @default.
• W2070301080 cites W1879327185 @default.
• W2070301080 cites W1967464880 @default.
• W2070301080 cites W1968937229 @default.
• W2070301080 cites W1970108896 @default.
• W2070301080 cites W1972899454 @default.
• W2070301080 cites W1976740826 @default.
• W2070301080 cites W1982216737 @default.
• W2070301080 cites W1987927755 @default.
• W2070301080 cites W1990675281 @default.
• W2070301080 cites W1991208268 @default.
• W2070301080 cites W1997999262 @default.
• W2070301080 cites W2002659179 @default.
• W2070301080 cites W2003772355 @default.
• W2070301080 cites W2004792969 @default.
• W2070301080 cites W2014311428 @default.
• W2070301080 cites W2022294369 @default.
• W2070301080 cites W2031259748 @default.
• W2070301080 cites W2038421461 @default.
• W2070301080 cites W2051592058 @default.
• W2070301080 cites W2052742260 @default.
• W2070301080 cites W2058519323 @default.
• W2070301080 cites W2059524588 @default.
• W2070301080 cites W2063865293 @default.
• W2070301080 cites W2065140753 @default.
• W2070301080 cites W2075401349 @default.
• W2070301080 cites W2076159058 @default.
• W2070301080 cites W2087689873 @default.
• W2070301080 cites W2089082840 @default.
• W2070301080 cites W2093852116 @default.
• W2070301080 cites W2105758687 @default.
• W2070301080 cites W2131897453 @default.
• W2070301080 cites W2133081366 @default.
• W2070301080 cites W2143595037 @default.
• W2070301080 cites W2144795344 @default.
• W2070301080 cites W2149746962 @default.
• W2070301080 cites W2155390548 @default.
• W2070301080 cites W2157566126 @default.
• W2070301080 cites W2167818155 @default.
• W2070301080 cites W2168079270 @default.
• W2070301080 doi "https://doi.org/10.1523/jneurosci.3345-09.2009" @default.
• W2070301080 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2775811" @default.
• W2070301080 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19793966" @default.
• W2070301080 hasPublicationYear "2009" @default.
• W2070301080 type Work @default.
• W2070301080 sameAs 2070301080 @default.
• W2070301080 citedByCount "201" @default.
• W2070301080 countsByYear W20703010802012 @default.
• W2070301080 countsByYear W20703010802013 @default.
• W2070301080 countsByYear W20703010802014 @default.
• W2070301080 countsByYear W20703010802015 @default.
• W2070301080 countsByYear W20703010802016 @default.
• W2070301080 countsByYear W20703010802017 @default.
• W2070301080 countsByYear W20703010802018 @default.
• W2070301080 countsByYear W20703010802019 @default.
• W2070301080 countsByYear W20703010802020 @default.
• W2070301080 countsByYear W20703010802021 @default.
• W2070301080 countsByYear W20703010802022 @default.
• W2070301080 countsByYear W20703010802023 @default.
• W2070301080 crossrefType "journal-article" @default.
• W2070301080 hasAuthorship W2070301080A5008674482 @default.
• W2070301080 hasAuthorship W2070301080A5009411980 @default.
• W2070301080 hasAuthorship W2070301080A5018156812 @default.
• W2070301080 hasAuthorship W2070301080A5032532137 @default.
• W2070301080 hasAuthorship W2070301080A5045363726 @default.
• W2070301080 hasAuthorship W2070301080A5046928489 @default.
• W2070301080 hasAuthorship W2070301080A5052932581 @default.
• W2070301080 hasAuthorship W2070301080A5057034557 @default.
• W2070301080 hasAuthorship W2070301080A5060699815 @default.
• W2070301080 hasAuthorship W2070301080A5062473042 @default.
• W2070301080 hasAuthorship W2070301080A5063630066 @default.
• W2070301080 hasAuthorship W2070301080A5067529915 @default.
• W2070301080 hasAuthorship W2070301080A5071434472 @default.
• W2070301080 hasAuthorship W2070301080A5076967941 @default.
• W2070301080 hasAuthorship W2070301080A5084141510 @default.

• next