| http://purl.uniprot.org/citations/25361083 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25361083 | http://www.w3.org/2000/01/rdf-schema#comment | "Mitochondrial dysfunction, often characterized by massive fission and other morphological abnormalities, is a well-known risk factor for Alzheimer's disease (AD). One causative mechanism underlying AD-associated mitochondrial dysfunction is thought to be amyloid-β (Aβ), yet the pathways between Aβ and mitochondrial dysfunction remain elusive. In this study, we report that CR6-interacting factor 1 (Crif1), a mitochondrial inner membrane protein, is a key player in Aβ-induced mitochondrial dysfunction. Specifically, we found that Crif1 levels were downregulated in the pathological regions of Tg6799 mice brains, wherein overexpressed Aβ undergoes self-aggregation. Downregulation of Crif1 was similarly observed in human AD brains as well as in SH-SY5Y cells treated with Aβ. In addition, knockdown of Crif1, using RNA interference, induced mitochondrial dysfunction with phenotypes similar to those observed in Aβ-treated cells. Conversely, Crif1 overexpression prevented Aβ-induced mitochondrial dysfunction and cell death. Finally, we show that Aβ-induced downregulation of Crif1 is mediated by enhanced reactive oxygen species (ROS) and ROS-dependent sumoylation of the transcription factor specificity protein 1 (Sp1). These results identify the ROS-Sp1-Crif1 pathway to be a new mechanism underlying Aβ-induced mitochondrial dysfunction and suggest that ROS-mediated downregulation of Crif1 is a crucial event in AD pathology. We propose that Crif1 may serve as a novel therapeutic target in the treatment of AD."xsd:string |
| http://purl.uniprot.org/citations/25361083 | http://purl.org/dc/terms/identifier | "doi:10.1038/cdd.2014.184"xsd:string |
| http://purl.uniprot.org/citations/25361083 | http://purl.uniprot.org/core/author | "Kim Y."xsd:string |
| http://purl.uniprot.org/citations/25361083 | http://purl.uniprot.org/core/author | "Kim K.S."xsd:string |
| http://purl.uniprot.org/citations/25361083 | http://purl.uniprot.org/core/author | "Shong M."xsd:string |
| http://purl.uniprot.org/citations/25361083 | http://purl.uniprot.org/core/author | "Ryu H."xsd:string |
| http://purl.uniprot.org/citations/25361083 | http://purl.uniprot.org/core/author | "Moon M."xsd:string |
| http://purl.uniprot.org/citations/25361083 | http://purl.uniprot.org/core/author | "Byun J."xsd:string |
| http://purl.uniprot.org/citations/25361083 | http://purl.uniprot.org/core/author | "Mook-Jung I."xsd:string |
| http://purl.uniprot.org/citations/25361083 | http://purl.uniprot.org/core/author | "Son S.M."xsd:string |
| http://purl.uniprot.org/citations/25361083 | http://purl.uniprot.org/core/author | "Hwang Y.J."xsd:string |
| http://purl.uniprot.org/citations/25361083 | http://purl.uniprot.org/core/author | "Cha M.Y."xsd:string |
| http://purl.uniprot.org/citations/25361083 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25361083 | http://purl.uniprot.org/core/name | "Cell Death Differ"xsd:string |
| http://purl.uniprot.org/citations/25361083 | http://purl.uniprot.org/core/pages | "959-973"xsd:string |
| http://purl.uniprot.org/citations/25361083 | http://purl.uniprot.org/core/title | "CR6-interacting factor 1 is a key regulator in Abeta-induced mitochondrial disruption and pathogenesis of Alzheimer's disease."xsd:string |
| http://purl.uniprot.org/citations/25361083 | http://purl.uniprot.org/core/volume | "22"xsd:string |
| http://purl.uniprot.org/citations/25361083 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25361083 |
| http://purl.uniprot.org/citations/25361083 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25361083 |
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| http://purl.uniprot.org/uniprot/#_Q9CR59-mappedCitation-25361083 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25361083 |
| http://purl.uniprot.org/uniprot/#_Q8TAE8-mappedCitation-25361083 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25361083 |
| http://purl.uniprot.org/uniprot/Q8TAE8 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/25361083 |
| http://purl.uniprot.org/uniprot/Q9CR59 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/25361083 |