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Lindersson, EK ; Hojrup, P ; Gai, WP ; Locker, D ; Martin, D ; Jensen, PH

Alpha-Synuclein filaments bind the transcriptional regulator HMGB-1

Neuroreport 15 (18) 2735-2739

par Administrateur - publié le

Abstract :

Abnormal accumulation of a-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 I (HMGB-1) as a ligand for a-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 a-synuclein filament-containing Lewy bodies isolated from brain tissue affected with dementia with Lewy bodies or Parkinson’s disease. Our results demonstrate that a-synuclein filaments hold the potential for disturbing the cellular gene expression as they can sequester a component involved in cellular transcription regulation.