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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2002-3-15
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pubmed:abstractText |
Mutations in the presenilin-1 (PS-1) gene account for a significant fraction of familial Alzheimer's disease. The biological function of PS-1 is not well understood. We report here that the proliferation-associated gene (PAG) product, a protein of the thioredoxin peroxidase family, interacts with PS-1. Microinjection of a plasmid expressing PAG into superior cervical ganglion (SCG) sympathetic neurons in primary cultures led to apoptosis. Microinjection of plasmids expressing wild-type PS-1 or a PS-1 mutant with a deletion of exon 10 (PS1dE10) by themselves had no effect on the survival of primary SCG neurons. However, co-injection of wild-type PS-1 with PAG prevented neuronal death, whereas co-injection with the mutant PS-1 did not affect PAG-induced apoptosis. Furthermore, overexpression of PAG accelerated SCG neuronal death induced by nerve growth factor deprivation. This sensitizing effect was also blocked by wild-type PS-1, but not by PS1dE10. These results establish an assay for studying the function of PS-1 in primary neurons, reveal the neurotoxicity of a thioredoxin peroxidase, demonstrate a neuroprotective activity of the wild-type PS-1, and suggest possible involvement of defective neuroprotection by PS-1 mutants in neurodegeneration.
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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/Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/PRDX1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PRDX3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PSEN1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Peroxidases,
http://linkedlifedata.com/resource/pubmed/chemical/Peroxiredoxin III,
http://linkedlifedata.com/resource/pubmed/chemical/Peroxiredoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Prdx1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Presenilin-1
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0969-9961
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pubmed:author |
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pubmed:copyrightInfo |
(c)2002 Elsevier Science (USA).
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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 |
126-38
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:11895366-Animals,
pubmed-meshheading:11895366-Apoptosis,
pubmed-meshheading:11895366-Cell Survival,
pubmed-meshheading:11895366-Cells, Cultured,
pubmed-meshheading:11895366-Exons,
pubmed-meshheading:11895366-Gene Deletion,
pubmed-meshheading:11895366-Gene Expression,
pubmed-meshheading:11895366-Heat-Shock Proteins,
pubmed-meshheading:11895366-Humans,
pubmed-meshheading:11895366-Kidney,
pubmed-meshheading:11895366-Membrane Proteins,
pubmed-meshheading:11895366-Neoplasm Proteins,
pubmed-meshheading:11895366-Nerve Growth Factors,
pubmed-meshheading:11895366-Neurons,
pubmed-meshheading:11895366-Peroxidases,
pubmed-meshheading:11895366-Peroxiredoxin III,
pubmed-meshheading:11895366-Peroxiredoxins,
pubmed-meshheading:11895366-Plasmids,
pubmed-meshheading:11895366-Presenilin-1,
pubmed-meshheading:11895366-Rats,
pubmed-meshheading:11895366-Superior Cervical Ganglion
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pubmed:year |
2002
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pubmed:articleTitle |
Presenilin-1 protects against neuronal apoptosis caused by its interacting protein PAG.
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pubmed:affiliation |
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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