Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 89-93 |
| Number of pages | 5 |
| Journal | Neuroscience Letters |
| Volume | 359(1-2) |
| Issue number | 1-2 |
| DOIs | |
| Publication status | Published - 08 Apr 2004 |
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Inhibition and fibril formation and toxicity of a fragment of alpha-synuclein by an N-methylated peptide analogue. / Bodles, A.M.; El-Agnaf, O.M.A.; Greer, Brett; Guthrie, D.J.S.; Irvine, Brent.
In: Neuroscience Letters, Vol. 359(1-2), No. 1-2, 08.04.2004, p. 89-93.Research output: Contribution to journal › Article
TY - JOUR
T1 - Inhibition and fibril formation and toxicity of a fragment of alpha-synuclein by an N-methylated peptide analogue
AU - Bodles, A.M.
AU - El-Agnaf, O.M.A.
AU - Greer, Brett
AU - Guthrie, D.J.S.
AU - Irvine, Brent
PY - 2004/4/8
Y1 - 2004/4/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=1842608890&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2003.12.077
DO - 10.1016/j.neulet.2003.12.077
M3 - Article
VL - 359(1-2)
SP - 89
EP - 93
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 1-2
ER -