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 language | English |
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Pages (from-to) | 89-93 |
Number of pages | 5 |
Journal | Neuroscience Letters |
Volume | 359 |
Issue number | 1-2 |
DOIs | |
Publication status | Published - Apr 8 2004 |
Externally published | Yes |
Keywords
- Amyloid
- Cytotoxicity
- Dementia with Lewy bodies
- MTT
- N-Methylated peptide
- Parkinson's disease
- α-synuclein
ASJC Scopus subject areas
- General Neuroscience