Ontology type: schema:ScholarlyArticle
2019-01-05
AUTHORSKathryn Cimdins, Hayley S. Waugh, Vicki Chrysostomou, M. Isabel G. Lopez Sanchez, Vanessa A. Johannsen, Mark J. Cook, Jonathan G. Crowston, Andrew F. Hill, James A. Duce, Ashley I. Bush, Ian A. Trounce
ABSTRACTMitochondrial complex I dysfunction is the most common respiratory chain defect in human disorders and a hotspot for neurodegenerative diseases. Amyloid precursor protein (APP) and its non-amyloidogenic processing products, in particular soluble APP α (sAPPα), have been shown to provide neuroprotection in models of neuronal injury; however, APP-mediated protection from acute mitochondrial injury has not been previously reported. Here, we use the plant-derived pesticide rotenone, a potent complex I-specific mitochondrial inhibitor, to discover neuroprotective effects of APP and sAPPα in vitro, in neuronal cell lines over-expressing APP, and in vivo, in a retinal neuronal rotenone toxicity mouse model. Our results show that APP over-expression is protective against rotenone toxicity in neurons via sAPPα through an autocrine/paracrine mechanism that involves the Pi3K/Akt pro-survival pathway. APP-/- mice exhibit greater susceptibility to retinal rotenone toxicity, while intravitreal delivery of sAPPα reduces inner retinal neuronal death in wild-type mice following rotenone challenge. We also show a significant decrease in human retinal expression of APP with age. These findings provide insights into the therapeutic potential of non-amyloidogenic processing of APP in complex I-related neurodegeneration. More... »
PAGES1-12
http://scigraph.springernature.com/pub.10.1007/s12035-018-1460-7
DOIhttp://dx.doi.org/10.1007/s12035-018-1460-7
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PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/30612335
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"https://doi.org/10.1007/s12035-018-1460-7",
"https://app.dimensions.ai/details/publication/pub.1111157346"
],
"sdDataset": "articles",
"sdDatePublished": "2019-04-11T08:35",
"sdLicense": "https://scigraph.springernature.com/explorer/license/",
"sdPublisher": {
"name": "Springer Nature - SN SciGraph project",
"type": "Organization"
},
"sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000312_0000000312/records_1298_00000000.jsonl",
"type": "ScholarlyArticle",
"url": "https://link.springer.com/10.1007%2Fs12035-018-1460-7"
}
]Download the RDF metadata as: json-ld nt turtle xml License info
JSON-LD is a popular format for linked data which is fully compatible with JSON.
curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s12035-018-1460-7'
N-Triples is a line-based linked data format ideal for batch operations.
curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s12035-018-1460-7'
Turtle is a human-readable linked data format.
curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s12035-018-1460-7'
RDF/XML is a standard XML format for linked data.
curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s12035-018-1460-7'
This table displays all metadata directly associated to this object as RDF triples.
309 TRIPLES
21 PREDICATES
77 URIs
18 LITERALS
7 BLANK NODES