Amyloidogenicity of rodent and human βA4 sequences

FEBS Letters

Dyrks, Thomas³  Beyreuther, Konrad¹  Dyrks, Elke¹  L. Masters, Colin² 

[1] Center for Molecular Biology Heidelberg, University Heidelberg, Heidelberg, Germany;Department of Pathology, University of Melbourne, Parkville, Victoria 3052, Australia;Research Laboratories of Schering AG, Berlin 65, Germany

关键词: A4CT;    βA4;    Radical;    Rodent sequence;    Aggregation;    Alzheimer's disease;   

DOI  :  10.1016/0014-5793(93)81399-K

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Previously we have shown that aggregation of the C-terminal 100 residues (A4CT) of the βA4 amyloid protein precursor (APP) and also of βA4 itself depends on the presence of metal-catalyzed oxidation systems [T. Dyrks et al. (1988) EMBO J. 7, 949-957]. We showed that aggregation of the amyloidogenic peptides induced by radical generation systems requires amino acid oxidation and protein cross-linking. Here we report that aggregation of A4CT and βA4 induced by radical generation systems involves oxidation of histidine, tyrosine and methionine residues. The roden βA4 sequence lacking the single tyrosine and one of the three histidine residues of human βA4 and a βA4 variant in which the tyrosine and the three histidine residues were replaced showed a reduced tendency for aggregation. Thus our results may explain why βA4 amyloid deposits could so far not been detected in the rodent brain.

【 授权许可】

Unknown