Abstract
Abnormal accumulation of alpha-synuclein filaments in Lewy bodies is a neuropathological hallmark of Parkinson's disease and sequestration of cellular protein into these protein aggregates may contribute to the degenerative process. We identified the transcriptional co-factor high mobility group protein 1 (HMGB-1) as a ligand for alpha-synuclein filaments by a filament spin-down technique, mass spectrometric peptide mapping and immunoblotting. HMGB-1 binds preferentially to aggregated alpha-synuclein and is present in alpha-synuclein filament-containing Lewy bodies isolated from brain tissue affected with dementia with Lewy bodies or Parkinson's disease. Our results demonstrate that alpha-synuclein filaments hold the potential for disturbing the cellular gene expression as they can sequester a component involved in cellular transcription regulation.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brain / metabolism
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Brain / pathology
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HMGB1 Protein / analysis
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HMGB1 Protein / chemistry
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HMGB1 Protein / metabolism*
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HMGB1 Protein / ultrastructure
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Humans
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Immunoblotting / methods
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Immunohistochemistry / methods
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Iodine Isotopes / metabolism
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Lewy Bodies / metabolism
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Lewy Body Disease / metabolism
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Ligands
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Microscopy, Immunoelectron / methods
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Nerve Tissue Proteins / analysis
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Nerve Tissue Proteins / metabolism*
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Nerve Tissue Proteins / ultrastructure
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Neurites / metabolism
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Neurons / cytology
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Neurons / metabolism
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Parkinson Disease / metabolism
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Peptide Mapping / methods
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Protein Binding
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Rats
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Recombinant Proteins / metabolism
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Synucleins
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alpha-Synuclein
Substances
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HMGB1 Protein
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Iodine Isotopes
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Ligands
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Nerve Tissue Proteins
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Recombinant Proteins
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SNCA protein, human
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Snca protein, rat
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Synucleins
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alpha-Synuclein