α-synuclein filaments bind the transcriptional regulator HMGB-1

E.K. Lindersson , P. Højrup , W.P. Gai , D. Locker (1) , D. Martin (1) , P.H. Jensen

1 CBM - Centre de biophysique moléculaire

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.

Domaines: Neurosciences

E.K. Lindersson, P. Højrup, W.P. Gai, D. Locker, D. Martin, et al.. α-synuclein filaments bind the transcriptional regulator HMGB-1. NeuroReport, 2004, 15, pp.2735-2739. ⟨hal-00088420⟩