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

Angela M. Bodles, Omar Ali El-Agnaf, Brett Greer, David J S Guthrie, G. Brent Irvine

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

α-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 α-synuclein is the minimum fragment that, like α-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 Aβ(25-35) inhibited the formation of fibrils by Aβ(25-35) and reduced its toxicity. We have now extended this concept to an amyloidogenic α-synuclein-based peptide. α-Synuclein(68-78), N-methylated at G1y73, was compared to non-methylated peptide. Whereas α-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
Issue number1-2
DOIs
Publication statusPublished - 8 Apr 2004
Externally publishedYes

Fingerprint

Synucleins
Peptides
Poisons
Amyloid
Neurodegenerative Diseases
Parkinson Disease
Cell Culture Techniques

Keywords

  • α-synuclein
  • Amyloid
  • Cytotoxicity
  • Dementia with Lewy bodies
  • MTT
  • N-Methylated peptide
  • Parkinson's disease

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Inhibition of fibril formation and toxicity of a fragment of α-synuclein by an N-methylated peptide analogue. / Bodles, Angela M.; Ali El-Agnaf, Omar; Greer, Brett; Guthrie, David J S; Irvine, G. Brent.

In: Neuroscience Letters, Vol. 359, No. 1-2, 08.04.2004, p. 89-93.

Research output: Contribution to journalArticle

Bodles, Angela M. ; Ali El-Agnaf, Omar ; Greer, Brett ; Guthrie, David J S ; Irvine, G. Brent. / Inhibition of fibril formation and toxicity of a fragment of α-synuclein by an N-methylated peptide analogue. In: Neuroscience Letters. 2004 ; Vol. 359, No. 1-2. pp. 89-93.
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