| http://purl.uniprot.org/citations/25485680 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25485680 | http://www.w3.org/2000/01/rdf-schema#comment | "Spinocerebellar ataxia type 28 (SCA28) is a neurodegenerative disease caused by mutations of the mitochondrial protease AFG3L2. The SCA28 mouse model, which is haploinsufficient for Afg3l2, exhibits a progressive decline in motor function and displays dark degeneration of Purkinje cells (PC-DCD) of mitochondrial origin. Here, we determined that mitochondria in cultured Afg3l2-deficient PCs ineffectively buffer evoked Ca²⁺ peaks, resulting in enhanced cytoplasmic Ca²⁺ concentrations, which subsequently triggers PC-DCD. This Ca²⁺-handling defect is the result of negative synergism between mitochondrial depolarization and altered organelle trafficking to PC dendrites in Afg3l2-mutant cells. In SCA28 mice, partial genetic silencing of the metabotropic glutamate receptor mGluR1 decreased Ca²⁺ influx in PCs and reversed the ataxic phenotype. Moreover, administration of the β-lactam antibiotic ceftriaxone, which promotes synaptic glutamate clearance, thereby reducing Ca²⁺ influx, improved ataxia-associated phenotypes in SCA28 mice when given either prior to or after symptom onset. Together, the results of this study indicate that ineffective mitochondrial Ca²⁺ handling in PCs underlies SCA28 pathogenesis and suggest that strategies that lower glutamate stimulation of PCs should be further explored as a potential treatment for SCA28 patients."xsd:string |
| http://purl.uniprot.org/citations/25485680 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci74770"xsd:string |
| http://purl.uniprot.org/citations/25485680 | http://purl.uniprot.org/core/author | "Drago I."xsd:string |
| http://purl.uniprot.org/citations/25485680 | http://purl.uniprot.org/core/author | "Casari G."xsd:string |
| http://purl.uniprot.org/citations/25485680 | http://purl.uniprot.org/core/author | "Maltecca F."xsd:string |
| http://purl.uniprot.org/citations/25485680 | http://purl.uniprot.org/core/author | "Quattrini A."xsd:string |
| http://purl.uniprot.org/citations/25485680 | http://purl.uniprot.org/core/author | "Podini P."xsd:string |
| http://purl.uniprot.org/citations/25485680 | http://purl.uniprot.org/core/author | "Mazza D."xsd:string |
| http://purl.uniprot.org/citations/25485680 | http://purl.uniprot.org/core/author | "Consolato F."xsd:string |
| http://purl.uniprot.org/citations/25485680 | http://purl.uniprot.org/core/author | "Young S.M. Jr."xsd:string |
| http://purl.uniprot.org/citations/25485680 | http://purl.uniprot.org/core/author | "Puliti A."xsd:string |
| http://purl.uniprot.org/citations/25485680 | http://purl.uniprot.org/core/author | "Bahr B.A."xsd:string |
| http://purl.uniprot.org/citations/25485680 | http://purl.uniprot.org/core/author | "Codazzi F."xsd:string |
| http://purl.uniprot.org/citations/25485680 | http://purl.uniprot.org/core/author | "Baseggio E."xsd:string |
| http://purl.uniprot.org/citations/25485680 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25485680 | http://purl.uniprot.org/core/name | "J Clin Invest"xsd:string |
| http://purl.uniprot.org/citations/25485680 | http://purl.uniprot.org/core/pages | "263-274"xsd:string |
| http://purl.uniprot.org/citations/25485680 | http://purl.uniprot.org/core/title | "Purkinje neuron Ca2+ influx reduction rescues ataxia in SCA28 model."xsd:string |
| http://purl.uniprot.org/citations/25485680 | http://purl.uniprot.org/core/volume | "125"xsd:string |
| http://purl.uniprot.org/citations/25485680 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25485680 |
| http://purl.uniprot.org/citations/25485680 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25485680 |
| http://purl.uniprot.org/uniprot/#_P97772-mappedCitation-25485680 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25485680 |
| http://purl.uniprot.org/uniprot/#_Q3V0U2-mappedCitation-25485680 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25485680 |
| http://purl.uniprot.org/uniprot/#_Q3UDQ7-mappedCitation-25485680 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25485680 |