A role for motoneuron subtype–selective ER stress in disease manifestations of FALS mice View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2009-05

AUTHORS

Smita Saxena, Erik Cabuy, Pico Caroni

ABSTRACT

The 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... »

PAGES

627-636

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nn.2297

DOI

http://dx.doi.org/10.1038/nn.2297

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1027273040

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19330001


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

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N-Triples is a line-based linked data format ideal for batch operations.

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Turtle is a human-readable linked data format.

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'


 

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