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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 |
2004-6-30
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pubmed:abstractText |
The accumulation of misfolded proteins in intracellular inclusions is a generic feature of neurodegenerative disorders. Although heavily ubiquitylated, the aggregated proteins are not degraded by the proteasomes. A possible reason for this phenomenon may be a modification of deposited proteins by transglutaminases forming gamma-glutamyl-epsilon-lysine (GGEL) cross-links between distinct proteins. Here, we show that the frequency of GGEL cross-links is an order of magnitude higher in Alzheimer's brain cortex than in age-matched or younger controls. This difference is due to the accumulation of GGEL cross-links in ubiquitin-immunopositive protein particles present in both Alzheimer's brains and those from aged individuals. The highly cross-linked protein aggregates show immunoreactivity to antibodies against tau and neurofilament proteins, and partially also to alpha-synuclein, indicating that these structures are inherent in Alzheimer's neurofibrillary tangles and Lewy bodies. Using mass sequence analysis, we identified the same six pairs of peptide sequences cross-linked in both senile and Alzheimer's specimens: Gln31 and Gln190 of HSP27 protein are cross-linked with Lys29 and Lys48 of ubiquitin and HSP27 therefore may cross-link two (poly)ubiquitin chains. One lysine residue of parkin and one of alpha-synuclein were also found to be cross-linked. The data suggest that cross-linking of (poly)ubiquitin moieties via HSP27 may have a role in the stabilization of the intraneuronal protein aggregates by interference with the proteasomal elimination of unfolded proteins.
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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/Dipeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamine,
http://linkedlifedata.com/resource/pubmed/chemical/HSP27 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HSPB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lysine,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neurofilament Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/SNCA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Synucleins,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-Synuclein,
http://linkedlifedata.com/resource/pubmed/chemical/epsilon-(gamma-glutamyl)-lysine,
http://linkedlifedata.com/resource/pubmed/chemical/parkin protein,
http://linkedlifedata.com/resource/pubmed/chemical/tau Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1530-6860
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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 |
1135-7
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15132984-Adult,
pubmed-meshheading:15132984-Aged,
pubmed-meshheading:15132984-Aged, 80 and over,
pubmed-meshheading:15132984-Alzheimer Disease,
pubmed-meshheading:15132984-Brain Chemistry,
pubmed-meshheading:15132984-Cerebral Cortex,
pubmed-meshheading:15132984-Chromatography, High Pressure Liquid,
pubmed-meshheading:15132984-Dipeptides,
pubmed-meshheading:15132984-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:15132984-Female,
pubmed-meshheading:15132984-Glutamine,
pubmed-meshheading:15132984-HSP27 Heat-Shock Proteins,
pubmed-meshheading:15132984-Heat-Shock Proteins,
pubmed-meshheading:15132984-Hippocampus,
pubmed-meshheading:15132984-Humans,
pubmed-meshheading:15132984-Inclusion Bodies,
pubmed-meshheading:15132984-Lysine,
pubmed-meshheading:15132984-Macromolecular Substances,
pubmed-meshheading:15132984-Male,
pubmed-meshheading:15132984-Neoplasm Proteins,
pubmed-meshheading:15132984-Nerve Tissue Proteins,
pubmed-meshheading:15132984-Neurofibrillary Tangles,
pubmed-meshheading:15132984-Neurofilament Proteins,
pubmed-meshheading:15132984-Plaque, Amyloid,
pubmed-meshheading:15132984-Proteasome Endopeptidase Complex,
pubmed-meshheading:15132984-Solubility,
pubmed-meshheading:15132984-Synucleins,
pubmed-meshheading:15132984-Ubiquitin,
pubmed-meshheading:15132984-Ubiquitin-Protein Ligases,
pubmed-meshheading:15132984-alpha-Synuclein,
pubmed-meshheading:15132984-tau Proteins
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pubmed:year |
2004
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pubmed:articleTitle |
Cross-linking of ubiquitin, HSP27, parkin, and alpha-synuclein by gamma-glutamyl-epsilon-lysine bonds in Alzheimer's neurofibrillary tangles.
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pubmed:affiliation |
Department of Psychiatry, Hungarian Academy of Sciences, Research Center for Molecular Medicine, University of Debrecen, Debrecen, Hungary. znemes@dote.hu
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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