| http://purl.uniprot.org/citations/17304350 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17304350 | http://www.w3.org/2000/01/rdf-schema#comment | "A primary pathologic component of Alzheimer's disease (AD) is the formation of neurofibrillary tangles composed of hyperphosphorylated tau (p-tau). Expediting the removal of these p-tau species may be a relevant therapeutic strategy. Here we report that inhibition of Hsp90 led to decreases in p-tau levels independent of heat shock factor 1 (HSF1) activation. A critical mediator of this mechanism was carboxy terminus of Hsp70-interacting protein (CHIP), a tau ubiquitin ligase. Cochaperones were also involved in Hsp90-mediated removal of p-tau, while those of the mature Hsp90 refolding complex prevented this effect. This is the first demonstration to our knowledge that blockade of the refolding pathway promotes p-tau turnover through degradation. We also show that peripheral administration of a novel Hsp90 inhibitor promoted selective decreases in p-tau species in a mouse model of tauopathy, further suggesting a central role for the Hsp90 complex in the pathogenesis of tauopathies. When taken in the context of known high-affinity Hsp90 complexes in affected regions of the AD brain, these data implicate a central role for Hsp90 in the development of AD and other tauopathies and may provide a rationale for the development of novel Hsp90-based therapeutic strategies."xsd:string |
| http://purl.uniprot.org/citations/17304350 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci29715"xsd:string |
| http://purl.uniprot.org/citations/17304350 | http://purl.uniprot.org/core/author | "Dickson D.W."xsd:string |
| http://purl.uniprot.org/citations/17304350 | http://purl.uniprot.org/core/author | "Eckman C.B."xsd:string |
| http://purl.uniprot.org/citations/17304350 | http://purl.uniprot.org/core/author | "Hutton M."xsd:string |
| http://purl.uniprot.org/citations/17304350 | http://purl.uniprot.org/core/author | "Kamal A."xsd:string |
| http://purl.uniprot.org/citations/17304350 | http://purl.uniprot.org/core/author | "Lundgren K."xsd:string |
| http://purl.uniprot.org/citations/17304350 | http://purl.uniprot.org/core/author | "Patterson C."xsd:string |
| http://purl.uniprot.org/citations/17304350 | http://purl.uniprot.org/core/author | "Petrucelli L."xsd:string |
| http://purl.uniprot.org/citations/17304350 | http://purl.uniprot.org/core/author | "Dickey C.A."xsd:string |
| http://purl.uniprot.org/citations/17304350 | http://purl.uniprot.org/core/author | "Bailey R.M."xsd:string |
| http://purl.uniprot.org/citations/17304350 | http://purl.uniprot.org/core/author | "Dunmore J."xsd:string |
| http://purl.uniprot.org/citations/17304350 | http://purl.uniprot.org/core/author | "Burrows F."xsd:string |
| http://purl.uniprot.org/citations/17304350 | http://purl.uniprot.org/core/author | "Ash P."xsd:string |
| http://purl.uniprot.org/citations/17304350 | http://purl.uniprot.org/core/author | "Klosak N."xsd:string |
| http://purl.uniprot.org/citations/17304350 | http://purl.uniprot.org/core/author | "Nahman N.S. Jr."xsd:string |
| http://purl.uniprot.org/citations/17304350 | http://purl.uniprot.org/core/author | "Shoraka S."xsd:string |
| http://purl.uniprot.org/citations/17304350 | http://purl.uniprot.org/core/author | "Zlatkovic J."xsd:string |
| http://purl.uniprot.org/citations/17304350 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17304350 | http://purl.uniprot.org/core/name | "J Clin Invest"xsd:string |
| http://purl.uniprot.org/citations/17304350 | http://purl.uniprot.org/core/pages | "648-658"xsd:string |
| http://purl.uniprot.org/citations/17304350 | http://purl.uniprot.org/core/title | "The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins."xsd:string |
| http://purl.uniprot.org/citations/17304350 | http://purl.uniprot.org/core/volume | "117"xsd:string |
| http://purl.uniprot.org/citations/17304350 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/17304350 |