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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2003-9-26
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pubmed:abstractText |
The mechanisms of neurodegeneration that result in human immunodeficiency virus (HIV) type 1 dementia have not yet been identified. Here, we report that HIV-infected macrophages secrete the zymogen matrix metalloproteinase-2 (MMP-2), which is activated by exposure to MT1-MMP on neurons. Stromal cell-derived factor 1 alpha (SDF-1), a chemokine overexpressed by astrocytes during HIV infection, was converted to a highly neurotoxic protein after precise proteolytic processing by active MMP-2, which removed the N-terminal tetrapeptide. Implantation of cleaved SDF-1(5-67) into the basal ganglia of mice resulted in neuronal death and inflammation with ensuing neurobehavioral deficits that were abrogated by neutralizing antibodies to SDF-1 and an MMP inhibitor drug. Hence, this study identifies a new in vivo neurotoxic pathway in which cleavage of a chemokine by an induced metalloproteinase results in neuronal apoptosis that leads to neurodegeneration.
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pubmed:commentsCorrections |
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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/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/CXCL12 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL12,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CXC,
http://linkedlifedata.com/resource/pubmed/chemical/Cxcl12 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Neurotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1097-6256
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1064-71
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:14502291-AIDS Dementia Complex,
pubmed-meshheading:14502291-Animals,
pubmed-meshheading:14502291-Antibodies,
pubmed-meshheading:14502291-Astrocytes,
pubmed-meshheading:14502291-Cell Line,
pubmed-meshheading:14502291-Chemokine CXCL12,
pubmed-meshheading:14502291-Chemokines, CXC,
pubmed-meshheading:14502291-Disease Models, Animal,
pubmed-meshheading:14502291-Encephalitis,
pubmed-meshheading:14502291-Enzyme Inhibitors,
pubmed-meshheading:14502291-HIV-1,
pubmed-meshheading:14502291-Humans,
pubmed-meshheading:14502291-Macrophages,
pubmed-meshheading:14502291-Matrix Metalloproteinase 2,
pubmed-meshheading:14502291-Mice,
pubmed-meshheading:14502291-Neostriatum,
pubmed-meshheading:14502291-Nerve Degeneration,
pubmed-meshheading:14502291-Neurotoxins,
pubmed-meshheading:14502291-Peptide Fragments
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pubmed:year |
2003
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pubmed:articleTitle |
HIV-induced metalloproteinase processing of the chemokine stromal cell derived factor-1 causes neurodegeneration.
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pubmed:affiliation |
Department of Clinical Neurosciences, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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