Inhibition and fibril formation and toxicity of a fragment of alpha-synuclein by an N-methylated peptide analogue
Data(s) |
08/04/2004
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Resumo |
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. |
Identificador |
http://dx.doi.org/10.1016/j.neulet.2003.12.077 http://www.scopus.com/inward/record.url?scp=1842608890&partnerID=8YFLogxK |
Idioma(s) |
eng |
Direitos |
info:eu-repo/semantics/restrictedAccess |
Fonte |
Bodles , A M , El-Agnaf , O M A , Greer , B , Guthrie , D J S & Irvine , B 2004 , ' Inhibition and fibril formation and toxicity of a fragment of alpha-synuclein by an N-methylated peptide analogue ' Neuroscience Letters , vol 359(1-2) , no. 1-2 , pp. 89-93 . DOI: 10.1016/j.neulet.2003.12.077 |
Palavras-Chave | #/dk/atira/pure/subjectarea/asjc/2800 #Neuroscience(all) |
Tipo |
article |