| http://purl.uniprot.org/citations/24599400 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24599400 | http://www.w3.org/2000/01/rdf-schema#comment | "Gaucher disease, a prevalent lysosomal storage disease (LSD), is caused by insufficient activity of acid β-glucosidase (GCase) and the resultant glucosylceramide (GC)/glucosylsphingosine (GS) accumulation in visceral organs (Type 1) and the central nervous system (Types 2 and 3). Recent clinical and genetic studies implicate a pathogenic link between Gaucher and neurodegenerative diseases. The aggregation and inclusion bodies of α-synuclein with ubiquitin are present in the brains of Gaucher disease patients and mouse models. Indirect evidence of β-amyloid pathology promoting α-synuclein fibrillation supports these pathogenic proteins as a common feature in neurodegenerative diseases. Here, multiple proteins are implicated in the pathogenesis of chronic neuronopathic Gaucher disease (nGD). Immunohistochemical and biochemical analyses showed significant amounts of β-amyloid and amyloid precursor protein (APP) aggregates in the cortex, hippocampus, stratum and substantia nigra of the nGD mice. APP aggregates were in neuronal cells and colocalized with α-synuclein signals. A majority of APP co-localized with the mitochondrial markers TOM40 and Cox IV; a small portion co-localized with the autophagy proteins, P62/LC3, and the lysosomal marker, LAMP1. In cultured wild-type brain cortical neural cells, the GCase-irreversible inhibitor, conduritol B epoxide (CBE), reproduced the APP/α-synuclein aggregation and the accumulation of GC/GS. Ultrastructural studies showed numerous larger-sized and electron-dense mitochondria in nGD cerebral cortical neural cells. Significant reductions of mitochondrial adenosine triphosphate production and oxygen consumption (28-40%) were detected in nGD brains and in CBE-treated neural cells. These studies implicate defective GCase function and GC/GS accumulation as risk factors for mitochondrial dysfunction and the multi-proteinopathies (α-synuclein-, APP- and Aβ-aggregates) in nGD."xsd:string |
| http://purl.uniprot.org/citations/24599400 | http://purl.org/dc/terms/identifier | "doi:10.1093/hmg/ddu105"xsd:string |
| http://purl.uniprot.org/citations/24599400 | http://purl.uniprot.org/core/author | "Sun Y."xsd:string |
| http://purl.uniprot.org/citations/24599400 | http://purl.uniprot.org/core/author | "Zhang W."xsd:string |
| http://purl.uniprot.org/citations/24599400 | http://purl.uniprot.org/core/author | "Setchell K.D."xsd:string |
| http://purl.uniprot.org/citations/24599400 | http://purl.uniprot.org/core/author | "Xu K."xsd:string |
| http://purl.uniprot.org/citations/24599400 | http://purl.uniprot.org/core/author | "Grabowski G.A."xsd:string |
| http://purl.uniprot.org/citations/24599400 | http://purl.uniprot.org/core/author | "Xue L."xsd:string |
| http://purl.uniprot.org/citations/24599400 | http://purl.uniprot.org/core/author | "Xu Y.H."xsd:string |
| http://purl.uniprot.org/citations/24599400 | http://purl.uniprot.org/core/author | "Witte D."xsd:string |
| http://purl.uniprot.org/citations/24599400 | http://purl.uniprot.org/core/author | "Quinn B."xsd:string |
| http://purl.uniprot.org/citations/24599400 | http://purl.uniprot.org/core/author | "Liou B."xsd:string |
| http://purl.uniprot.org/citations/24599400 | http://purl.uniprot.org/core/author | "Li R.H."xsd:string |
| http://purl.uniprot.org/citations/24599400 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24599400 | http://purl.uniprot.org/core/name | "Hum Mol Genet"xsd:string |
| http://purl.uniprot.org/citations/24599400 | http://purl.uniprot.org/core/pages | "3943-3957"xsd:string |
| http://purl.uniprot.org/citations/24599400 | http://purl.uniprot.org/core/title | "Multiple pathogenic proteins implicated in neuronopathic Gaucher disease mice."xsd:string |
| http://purl.uniprot.org/citations/24599400 | http://purl.uniprot.org/core/volume | "23"xsd:string |
| http://purl.uniprot.org/citations/24599400 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/24599400 |
| http://purl.uniprot.org/citations/24599400 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/24599400 |
| http://purl.uniprot.org/uniprot/#_A0A0G2JDK2-mappedCitation-24599400 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24599400 |
| http://purl.uniprot.org/uniprot/#_P17439-mappedCitation-24599400 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24599400 |
| http://purl.uniprot.org/uniprot/A0A0G2JDK2 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/24599400 |
| http://purl.uniprot.org/uniprot/P17439 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/24599400 |