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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2003-9-1
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pubmed:abstractText |
Neuronal death in cerebral ischemia is largely due to excitotoxic mechanisms, which are known to activate the c-Jun N-terminal kinase (JNK) pathway. We have evaluated the neuroprotective power of a cell-penetrating, protease-resistant peptide that blocks the access of JNK to many of its targets. We obtained strong protection in two models of middle cerebral artery occlusion (MCAO): transient occlusion in adult mice and permanent occlusion in 14-d-old rat pups. In the first model, intraventricular administration as late as 6 h after occlusion reduced the lesion volume by more than 90% for at least 14 d and prevented behavioral consequences. In the second model, systemic delivery reduced the lesion by 78% and 49% at 6 and 12 h after ischemia, respectively. Protection correlated with prevention of an increase in c-Jun activation and c-Fos transcription. In view of its potency and long therapeutic window, this protease-resistant peptide is a promising neuroprotective agent for stroke.
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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/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Gene Products, tat,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Mapk8ip protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Mapk8ip protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/N-Methylaspartate,
http://linkedlifedata.com/resource/pubmed/chemical/Neuroprotective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1078-8956
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
9
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1180-6
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12937412-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:12937412-Animals,
pubmed-meshheading:12937412-Behavior, Animal,
pubmed-meshheading:12937412-Brain Ischemia,
pubmed-meshheading:12937412-Carrier Proteins,
pubmed-meshheading:12937412-Cells, Cultured,
pubmed-meshheading:12937412-Enzyme Inhibitors,
pubmed-meshheading:12937412-Excitatory Amino Acid Agonists,
pubmed-meshheading:12937412-Gene Products, tat,
pubmed-meshheading:12937412-Genes, fos,
pubmed-meshheading:12937412-Infarction, Middle Cerebral Artery,
pubmed-meshheading:12937412-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:12937412-Male,
pubmed-meshheading:12937412-Mice,
pubmed-meshheading:12937412-Mice, Inbred ICR,
pubmed-meshheading:12937412-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12937412-N-Methylaspartate,
pubmed-meshheading:12937412-Neurons,
pubmed-meshheading:12937412-Neuroprotective Agents,
pubmed-meshheading:12937412-Peptides,
pubmed-meshheading:12937412-Rats,
pubmed-meshheading:12937412-Recombinant Proteins
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pubmed:year |
2003
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pubmed:articleTitle |
A peptide inhibitor of c-Jun N-terminal kinase protects against excitotoxicity and cerebral ischemia.
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pubmed:affiliation |
Institut de Biologie Cellulaire et de Morphologie, Université de Lausanne, Rue du Bugnon 9, CH-1005, Switzerland. Tiziana.Borsello@ibcm.unil.ch
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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