Matches in SemOpenAlex for { <https://semopenalex.org/work/W2959529296> ?p ?o ?g. }
Showing items 1 to 74 of
74
with 100 items per page.
- W2959529296 abstract "Amyotrophic Lateral Sclerosis (ALS) is the most commonly occurring motor neuron disease that is fatal and incurable. Motor neurons are markedly vulnerable to excitotoxicity mostly from over-stimulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptors and are principal targets in ALS. Interferon-gamma (IFN-γ), a pro-inflammatory cytokine, can independently cause neuronal dysfunction by triggering calcium influx through a calcium-permeable complex of IFN-γ receptor 1 (IFN-γR1) subunit and AMPAR subunit Glutamate Receptor 1 (GluR1). This receptor complex is formed via a non-canonical neuron-specific IFN-γ pathway. In this study, we explore the expression of the non-canonical IFN-γ pathway’s key participants – the upstream targets: IFN-γR1 and GluR1, and the downstream players: Janus Kinase 1(JAK1), Signal Transducer and Activator of Transcription (STAT1), and Protein Kinase A (PKA) – for the first time in the hSOD1G93A ALS mouse model. Elevated IFN-γR1 protein expression was observed in motor neurons of both presymptomatic and symptomatic hSOD1G93A, while GluR1 protein levels were higher only in the symptomatic ALS mice ex vivo. The expression of the downstream participants, namely JAK1 and STAT1, were unchanged irrespective of age group and genotype, while one of PKA’s catalytic subunits was downregulated at transcript level in hSOD1G93A mice. In in vitro system involving primary motor neuron-enriched co-cultures representing the embryonic stage, IFN-γR1 and GluR1 were similarly expressed in both hSOD1G93A mice and non-transgenic control mice.We, also, determined the direct effects of IFN-γ alone or in the presence of an excitotoxic agent, kainate, on motor neuron survival in vitro. IFN-γ was weakly neurotoxic on the embryonic motor neurons and did not influence kainate-mediated excitotoxicity. In conclusion, increased IFN-γR1 in motor neurons of adult hSOD1G93A mice can most likely sensitize the neurons to excitotoxic insults involving GluR1 and/or pathways mediatedby IFN-γ, thus, serving as a potential direct link between neurodegeneration and inflammation in ALS." @default.
- W2959529296 created "2019-07-23" @default.
- W2959529296 creator A5090095116 @default.
- W2959529296 date "2019-01-01" @default.
- W2959529296 modified "2023-09-25" @default.
- W2959529296 title "Non-canonical neuron-specific interferon-gamma pathway in the hSOD1G93A mouse model of amyotrophic lateral sclerosis" @default.
- W2959529296 doi "https://doi.org/10.22032/dbt.38307" @default.
- W2959529296 hasPublicationYear "2019" @default.
- W2959529296 type Work @default.
- W2959529296 sameAs 2959529296 @default.
- W2959529296 citedByCount "0" @default.
- W2959529296 crossrefType "dissertation" @default.
- W2959529296 hasAuthorship W2959529296A5090095116 @default.
- W2959529296 hasConcept C104292427 @default.
- W2959529296 hasConcept C104317684 @default.
- W2959529296 hasConcept C126322002 @default.
- W2959529296 hasConcept C160268369 @default.
- W2959529296 hasConcept C169760540 @default.
- W2959529296 hasConcept C170493617 @default.
- W2959529296 hasConcept C185592680 @default.
- W2959529296 hasConcept C2776752467 @default.
- W2959529296 hasConcept C2779134260 @default.
- W2959529296 hasConcept C2780596555 @default.
- W2959529296 hasConcept C2780775167 @default.
- W2959529296 hasConcept C2781012912 @default.
- W2959529296 hasConcept C55493867 @default.
- W2959529296 hasConcept C61174792 @default.
- W2959529296 hasConcept C71924100 @default.
- W2959529296 hasConcept C86803240 @default.
- W2959529296 hasConcept C95444343 @default.
- W2959529296 hasConceptScore W2959529296C104292427 @default.
- W2959529296 hasConceptScore W2959529296C104317684 @default.
- W2959529296 hasConceptScore W2959529296C126322002 @default.
- W2959529296 hasConceptScore W2959529296C160268369 @default.
- W2959529296 hasConceptScore W2959529296C169760540 @default.
- W2959529296 hasConceptScore W2959529296C170493617 @default.
- W2959529296 hasConceptScore W2959529296C185592680 @default.
- W2959529296 hasConceptScore W2959529296C2776752467 @default.
- W2959529296 hasConceptScore W2959529296C2779134260 @default.
- W2959529296 hasConceptScore W2959529296C2780596555 @default.
- W2959529296 hasConceptScore W2959529296C2780775167 @default.
- W2959529296 hasConceptScore W2959529296C2781012912 @default.
- W2959529296 hasConceptScore W2959529296C55493867 @default.
- W2959529296 hasConceptScore W2959529296C61174792 @default.
- W2959529296 hasConceptScore W2959529296C71924100 @default.
- W2959529296 hasConceptScore W2959529296C86803240 @default.
- W2959529296 hasConceptScore W2959529296C95444343 @default.
- W2959529296 hasLocation W29595292961 @default.
- W2959529296 hasOpenAccess W2959529296 @default.
- W2959529296 hasPrimaryLocation W29595292961 @default.
- W2959529296 hasRelatedWork W1966077031 @default.
- W2959529296 hasRelatedWork W1973163231 @default.
- W2959529296 hasRelatedWork W1974804087 @default.
- W2959529296 hasRelatedWork W1987362442 @default.
- W2959529296 hasRelatedWork W2009384982 @default.
- W2959529296 hasRelatedWork W2017863037 @default.
- W2959529296 hasRelatedWork W2020046561 @default.
- W2959529296 hasRelatedWork W2024431507 @default.
- W2959529296 hasRelatedWork W2080732549 @default.
- W2959529296 hasRelatedWork W2097465597 @default.
- W2959529296 hasRelatedWork W2106991692 @default.
- W2959529296 hasRelatedWork W2140403305 @default.
- W2959529296 hasRelatedWork W2169769531 @default.
- W2959529296 hasRelatedWork W2339648830 @default.
- W2959529296 hasRelatedWork W2572928470 @default.
- W2959529296 hasRelatedWork W2792385954 @default.
- W2959529296 hasRelatedWork W2804712669 @default.
- W2959529296 hasRelatedWork W2901664246 @default.
- W2959529296 hasRelatedWork W2908475137 @default.
- W2959529296 hasRelatedWork W2936551526 @default.
- W2959529296 isParatext "false" @default.
- W2959529296 isRetracted "false" @default.
- W2959529296 magId "2959529296" @default.
- W2959529296 workType "dissertation" @default.