Inhibition and fibril formation and toxicity of a fragment of alpha-synuclein by an N-methylated peptide analogue

A.M. Bodles, O.M.A. El-Agnaf, Brett Greer, D.J.S. Guthrie, Brent Irvine

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)

Abstract

Alpha-synuclein has been linked to amyloidogenesis in Parkinson's disease and other neurodegenerative disorders. We have previously shown that a peptide comprising residues 68-78 of alpha-synuclein is the minimum fragment that, like alpha-synuclein itself, forms amyloid fibrils and exhibits toxicity towards cells in culture. Hughes et al. [J. Biol. Chem. 275 (2000) 25109] showed that an N-methylated derivative of Abeta(25-35) inhibited the formation of fibrils by Abeta(25-35) and reduced its toxicity. We have now extended this concept to an amyloidogenic alpha-synuclein-based peptide. Alpha-synuclein(68-78), N-methylated at G1y73, was compared to non-methylated peptide. Whereas alpha-synuclein(68-78) formed fibrils and was toxic to cells, the N-methylated analogue had neither of these properties. Moreover, an equimolar mixture of the non-methylated and methylated peptides formed very few fibrils and toxicity was markedly reduced.
Original languageEnglish
Pages (from-to)89-93
Number of pages5
JournalNeuroscience Letters
Volume359(1-2)
Issue number1-2
DOIs
Publication statusPublished - 08 Apr 2004

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Inhibition and fibril formation and toxicity of a fragment of alpha-synuclein by an N-methylated peptide analogue'. Together they form a unique fingerprint.

Cite this