| http://purl.uniprot.org/citations/23962722 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23962722 | http://www.w3.org/2000/01/rdf-schema#comment | "The accumulation of hyperphosphorylated tau in neurofibrillary tangles (NFTs) is a neuropathological hallmark of tauopathies, including Alzheimer's disease (AD) and chronic traumatic encephalopathy, but effective therapies directly targeting the tau protein are currently lacking. Herein, we describe a novel mechanism in which the acetylation of tau on KXGS motifs inhibits phosphorylation on this same motif, and also prevents tau aggregation. Using a site-specific antibody to detect acetylation of KXGS motifs, we demonstrate that these sites are hypoacetylated in patients with AD, as well as a mouse model of tauopathy, suggesting that loss of acetylation on KXGS motifs renders tau vulnerable to pathogenic insults. Furthermore, we identify histone deacetylase 6 (HDAC6) as the enzyme responsible for the deacetylation of these residues, and provide proof of concept that acute treatment with a selective and blood-brain barrier-permeable HDAC6 inhibitor enhances acetylation and decreases phosphorylation on tau's KXGS motifs in vivo. As such, we have uncovered a novel therapeutic pathway that can be manipulated to block the formation of pathogenic tau species in disease."xsd:string |
| http://purl.uniprot.org/citations/23962722 | http://purl.org/dc/terms/identifier | "doi:10.1093/hmg/ddt402"xsd:string |
| http://purl.uniprot.org/citations/23962722 | http://purl.uniprot.org/core/author | "Cook C."xsd:string |
| http://purl.uniprot.org/citations/23962722 | http://purl.uniprot.org/core/author | "Davis M."xsd:string |
| http://purl.uniprot.org/citations/23962722 | http://purl.uniprot.org/core/author | "Dickson D."xsd:string |
| http://purl.uniprot.org/citations/23962722 | http://purl.uniprot.org/core/author | "Petrucelli L."xsd:string |
| http://purl.uniprot.org/citations/23962722 | http://purl.uniprot.org/core/author | "Carlomagno Y."xsd:string |
| http://purl.uniprot.org/citations/23962722 | http://purl.uniprot.org/core/author | "DeTure M."xsd:string |
| http://purl.uniprot.org/citations/23962722 | http://purl.uniprot.org/core/author | "Gendron T.F."xsd:string |
| http://purl.uniprot.org/citations/23962722 | http://purl.uniprot.org/core/author | "Dunmore J."xsd:string |
| http://purl.uniprot.org/citations/23962722 | http://purl.uniprot.org/core/author | "Jarpe M."xsd:string |
| http://purl.uniprot.org/citations/23962722 | http://purl.uniprot.org/core/author | "Scheffel K."xsd:string |
| http://purl.uniprot.org/citations/23962722 | http://purl.uniprot.org/core/author | "Stetler C."xsd:string |
| http://purl.uniprot.org/citations/23962722 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/23962722 | http://purl.uniprot.org/core/name | "Hum Mol Genet"xsd:string |
| http://purl.uniprot.org/citations/23962722 | http://purl.uniprot.org/core/pages | "104-116"xsd:string |
| http://purl.uniprot.org/citations/23962722 | http://purl.uniprot.org/core/title | "Acetylation of the KXGS motifs in tau is a critical determinant in modulation of tau aggregation and clearance."xsd:string |
| http://purl.uniprot.org/citations/23962722 | http://purl.uniprot.org/core/volume | "23"xsd:string |
| http://purl.uniprot.org/citations/23962722 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23962722 |
| http://purl.uniprot.org/citations/23962722 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23962722 |
| http://purl.uniprot.org/uniprot/Q09472#attribution-4577433C2D78A6D6FF83D26424BC64E4 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/23962722 |
| http://purl.uniprot.org/uniprot/Q9UBN7#attribution-6211ABA005D0937A9FC0D2048C8471CC | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/23962722 |
| http://purl.uniprot.org/uniprot/Q9Z2V5#attribution-6211ABA005D0937A9FC0D2048C8471CC | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/23962722 |
| http://purl.uniprot.org/uniprot/#_A0A0A0MQC7-mappedCitation-23962722 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23962722 |