| http://purl.uniprot.org/citations/23509247 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23509247 | http://www.w3.org/2000/01/rdf-schema#comment | "Fragile X syndrome (FXS) is the most common inherited form of autism and intellectual disability and is caused by the silencing of a single gene, fragile X mental retardation 1 (Fmr1). The Fmr1 KO mouse displays phenotypes similar to symptoms in the human condition--including hyperactivity, repetitive behaviors, and seizures--as well as analogous abnormalities in the density of dendritic spines. Here we take a hypothesis-driven, mechanism-based approach to the search for an effective therapy for FXS. We hypothesize that a treatment that rescues the dendritic spine defect in Fmr1 KO mice may also ameliorate autism-like behavioral symptoms. Thus, we targeted a protein that regulates spines through modulation of actin cytoskeleton dynamics: p21-activated kinase (PAK). Our results demonstrate that a potent small molecule inhibitor of group I PAKs reverses dendritic spine phenotypes in Fmr1 KO mice. Moreover, this PAK inhibitor--which we call FRAX486--also rescues seizures and behavioral abnormalities such as hyperactivity and repetitive movements, thereby supporting the hypothesis that a drug treatment that reverses the spine abnormalities can also treat neurological and behavioral symptoms. Finally, a single administration of FRAX486 is sufficient to rescue all of these phenotypes in adult Fmr1 KO mice, demonstrating the potential for rapid, postdiagnostic therapy in adults with FXS."xsd:string |
| http://purl.uniprot.org/citations/23509247 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1219383110"xsd:string |
| http://purl.uniprot.org/citations/23509247 | http://purl.uniprot.org/core/author | "Campbell D.A."xsd:string |
| http://purl.uniprot.org/citations/23509247 | http://purl.uniprot.org/core/author | "Choi S.Y."xsd:string |
| http://purl.uniprot.org/citations/23509247 | http://purl.uniprot.org/core/author | "Vollrath B."xsd:string |
| http://purl.uniprot.org/citations/23509247 | http://purl.uniprot.org/core/author | "Tonegawa S."xsd:string |
| http://purl.uniprot.org/citations/23509247 | http://purl.uniprot.org/core/author | "Dolan B.M."xsd:string |
| http://purl.uniprot.org/citations/23509247 | http://purl.uniprot.org/core/author | "Ko H.Y."xsd:string |
| http://purl.uniprot.org/citations/23509247 | http://purl.uniprot.org/core/author | "Govindarajan A."xsd:string |
| http://purl.uniprot.org/citations/23509247 | http://purl.uniprot.org/core/author | "Lin G.G."xsd:string |
| http://purl.uniprot.org/citations/23509247 | http://purl.uniprot.org/core/author | "Shankaranarayana Rao B.S."xsd:string |
| http://purl.uniprot.org/citations/23509247 | http://purl.uniprot.org/core/author | "Duron S.G."xsd:string |
| http://purl.uniprot.org/citations/23509247 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23509247 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/23509247 | http://purl.uniprot.org/core/pages | "5671-5676"xsd:string |
| http://purl.uniprot.org/citations/23509247 | http://purl.uniprot.org/core/title | "Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486."xsd:string |
| http://purl.uniprot.org/citations/23509247 | http://purl.uniprot.org/core/volume | "110"xsd:string |
| http://purl.uniprot.org/citations/23509247 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23509247 |
| http://purl.uniprot.org/citations/23509247 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23509247 |
| http://purl.uniprot.org/uniprot/P35922#attribution-5C4E31264CA087BEB365B3A7E94744B0 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/23509247 |
| http://purl.uniprot.org/uniprot/Q8BTW9#attribution-5C4E31264CA087BEB365B3A7E94744B0 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/23509247 |
| http://purl.uniprot.org/uniprot/Q8BTW9#attribution-99700BCEC337EDFC4D7A92C34073A5D6 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/23509247 |
| http://purl.uniprot.org/uniprot/Q8CIN4#attribution-5C4E31264CA087BEB365B3A7E94744B0 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/23509247 |
| http://purl.uniprot.org/uniprot/Q8CIN4#attribution-99700BCEC337EDFC4D7A92C34073A5D6 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/23509247 |