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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2011-4-11
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pubmed:abstractText |
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that primarily affects motoneurons in the brain and spinal cord. Dominant mutations in superoxide dismutase-1 (SOD1) cause a familial form of ALS. Mutant SOD1-damaged glial cells contribute to ALS pathogenesis by releasing neurotoxic factors, but the mechanistic basis of the motoneuron-specific elimination is poorly understood. Here, we describe a motoneuron-selective death pathway triggered by activation of lymphotoxin-? receptor (LT-?R) by LIGHT, and operating by a novel signaling scheme. We show that astrocytes expressing mutant SOD1 mediate the selective death of motoneurons through the proinflammatory cytokine interferon-? (IFN?), which activates the LIGHT-LT-?R death pathway. The expression of LIGHT and LT-?R by motoneurons in vivo correlates with the preferential expression of IFN? by motoneurons and astrocytes at disease onset and symptomatic stage in ALS mice. Importantly, the genetic ablation of Light in an ALS mouse model retards progression, but not onset, of the disease and increases lifespan. We propose that IFN? contributes to a cross-talk between motoneurons and astrocytes causing the selective loss of some motoneurons following activation of the LIGHT-induced death pathway.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Fas protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphotoxin beta Receptor,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase,
http://linkedlifedata.com/resource/pubmed/chemical/Tnfsf14 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor Ligand...,
http://linkedlifedata.com/resource/pubmed/chemical/superoxide dismutase 1
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1476-5403
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
754-68
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pubmed:meshHeading |
pubmed-meshheading:21072055-Amyotrophic Lateral Sclerosis,
pubmed-meshheading:21072055-Animals,
pubmed-meshheading:21072055-Antigens, CD95,
pubmed-meshheading:21072055-Astrocytes,
pubmed-meshheading:21072055-Caspases,
pubmed-meshheading:21072055-Cell Death,
pubmed-meshheading:21072055-Cell Survival,
pubmed-meshheading:21072055-Cells, Cultured,
pubmed-meshheading:21072055-Enzyme Activation,
pubmed-meshheading:21072055-Gene Deletion,
pubmed-meshheading:21072055-Humans,
pubmed-meshheading:21072055-Interferon-gamma,
pubmed-meshheading:21072055-Lymphotoxin beta Receptor,
pubmed-meshheading:21072055-Mice,
pubmed-meshheading:21072055-Mice, Inbred C57BL,
pubmed-meshheading:21072055-Mice, Knockout,
pubmed-meshheading:21072055-Motor Neurons,
pubmed-meshheading:21072055-Mutation, Missense,
pubmed-meshheading:21072055-Rats,
pubmed-meshheading:21072055-Rats, Sprague-Dawley,
pubmed-meshheading:21072055-Signal Transduction,
pubmed-meshheading:21072055-Superoxide Dismutase,
pubmed-meshheading:21072055-Tumor Necrosis Factor Ligand Superfamily Member 14
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pubmed:year |
2011
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pubmed:articleTitle |
IFN? triggers a LIGHT-dependent selective death of motoneurons contributing to the non-cell-autonomous effects of mutant SOD1.
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pubmed:affiliation |
INSERM-Avenir team, The Mediterranean Institute of Neurobiology, Inmed. Marseille Cedex 09, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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