Ontology type: schema:ScholarlyArticle
2009-05
AUTHORSSmita Saxena, Erik Cabuy, Pico Caroni
ABSTRACTThe mechanisms underlying disease manifestations in neurodegeneration remain unclear, but their understanding is critical to devising effective therapies. We carry out a longitudinal analysis in vivo of identified motoneurons selectively vulnerable (VUL) or resistant (RES) to motoneuron disease (amyotrophic lateral sclerosis, ALS) and show that subtype-selective endoplasmic reticulum (ER) stress responses influence disease manifestations. VUL motoneurons were selectively prone to ER stress and showed gradually upregulated ER stress markers from birth on in three mouse models of familial ALS (FALS). 25-30 days before the earliest denervations, ubiquitin signals increased in both VUL and RES motoneurons, but an unfolded protein response coupled with microglial activation was initiated selectively in VUL motoneurons. This transition was followed by selective axonal degeneration and spreading stress. The ER stress-protective agent salubrinal attenuated disease manifestations and delayed progression, whereas chronic enhancement of ER stress promoted disease. Thus, whereas all motoneurons are preferentially affected in ALS, ER stress responses in specific motoneuron subtypes influence the progressive manifestations of weakening and paralysis. More... »
PAGES627-636
http://scigraph.springernature.com/pub.10.1038/nn.2297
DOIhttp://dx.doi.org/10.1038/nn.2297
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PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/19330001
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curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nn.2297'
RDF/XML is a standard XML format for linked data.
curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nn.2297'
This table displays all metadata directly associated to this object as RDF triples.
323 TRIPLES
21 PREDICATES
99 URIs
43 LITERALS
31 BLANK NODES