| http://purl.uniprot.org/citations/37838947 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/37838947 | http://www.w3.org/2000/01/rdf-schema#comment | "Anomalous aggregation of α-synuclein (α-Syn) is a pathological hallmark of many degenerative synucleinopathies including Lewy body dementia (LBD) and Parkinson's disease (PD). Despite its strong link to disease, the precise molecular mechanisms that link α-Syn aggregation to neurodegeneration have yet to be elucidated. Here, we find that elevated α-Syn leads to an increase in the plasma membrane (PM) phosphoinositide PI(4,5)P2, which precipitates α-Syn aggregation and drives toxic increases in mitochondrial Ca2+ and reactive oxygen species leading to neuronal death. Upstream of this toxic signaling pathway is PIP5K1γ, whose abundance and localization is enhanced at the PM by α-Syn-dependent increases in ARF6. Selective inhibition of PIP5K1γ or knockout of ARF6 in neurons rescues α-Syn aggregation and cellular phenotypes of toxicity. Collectively, our data suggest that modulation of phosphoinositide metabolism may be a therapeutic target to slow neurodegeneration for PD and other related neurodegenerative disorders."xsd:string |
| http://purl.uniprot.org/citations/37838947 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.celrep.2023.113244"xsd:string |
| http://purl.uniprot.org/citations/37838947 | http://purl.uniprot.org/core/author | "Dickson E.J."xsd:string |
| http://purl.uniprot.org/citations/37838947 | http://purl.uniprot.org/core/author | "Casas M."xsd:string |
| http://purl.uniprot.org/citations/37838947 | http://purl.uniprot.org/core/author | "Cologna S.M."xsd:string |
| http://purl.uniprot.org/citations/37838947 | http://purl.uniprot.org/core/author | "Simo S."xsd:string |
| http://purl.uniprot.org/citations/37838947 | http://purl.uniprot.org/core/author | "Dixon R.E."xsd:string |
| http://purl.uniprot.org/citations/37838947 | http://purl.uniprot.org/core/author | "Kutchukian C."xsd:string |
| http://purl.uniprot.org/citations/37838947 | http://purl.uniprot.org/core/author | "Pergande M.R."xsd:string |
| http://purl.uniprot.org/citations/37838947 | http://purl.uniprot.org/core/author | "Horvath J.D."xsd:string |
| http://purl.uniprot.org/citations/37838947 | http://purl.uniprot.org/core/author | "Sanchez S.C."xsd:string |
| http://purl.uniprot.org/citations/37838947 | http://purl.uniprot.org/core/date | "2023"xsd:gYear |
| http://purl.uniprot.org/citations/37838947 | http://purl.uniprot.org/core/name | "Cell Rep"xsd:string |
| http://purl.uniprot.org/citations/37838947 | http://purl.uniprot.org/core/pages | "113244"xsd:string |
| http://purl.uniprot.org/citations/37838947 | http://purl.uniprot.org/core/title | "alpha-Synuclein-dependent increases in PIP5K1gamma drive inositol signaling to promote neurotoxicity."xsd:string |
| http://purl.uniprot.org/citations/37838947 | http://purl.uniprot.org/core/volume | "42"xsd:string |
| http://purl.uniprot.org/citations/37838947 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/37838947 |
| http://purl.uniprot.org/citations/37838947 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/37838947 |
| http://purl.uniprot.org/uniprot/#_Q04742-mappedCitation-37838947 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37838947 |
| http://purl.uniprot.org/uniprot/#_P62331-mappedCitation-37838947 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37838947 |
| http://purl.uniprot.org/uniprot/#_Q3U0D7-mappedCitation-37838947 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37838947 |
| http://purl.uniprot.org/uniprot/Q04742 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/37838947 |
| http://purl.uniprot.org/uniprot/P62331 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/37838947 |
| http://purl.uniprot.org/uniprot/Q3U0D7 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/37838947 |