Copper-mediated amyloid-beta toxicity is associated with an intermolecular histidine bridge.

@article{Smith2006CoppermediatedAT,
  title={Copper-mediated amyloid-beta toxicity is associated with an intermolecular histidine bridge.},
  author={David P Smith and Danielle G Smith and Cyril C. Curtain and John F. Boas and John R. Pilbrow and Giuseppe Donato Ciccotosto and Tong-Lay Lau and Deborah J Tew and Keyla Perez and John D Wade and Ashley I. Bush and Simon C Drew and Frances Separovic and Colin L. Masters and Roberto Cappai and Kevin Jeffrey Barnham},
  journal={The Journal of biological chemistry},
  year={2006},
  volume={281 22},
  pages={15145-54}
}
Amyloid-beta peptide (Abeta) is pivotal to the pathogenesis of Alzheimer disease. Here we report the formation of a toxic Abeta-Cu2+ complex formed via a histidine-bridged dimer, as observed at Cu2+/peptide ratios of >0.6:1 by EPR spectroscopy. The toxicity of the Abeta-Cu2+ complex to cultured primary cortical neurons was attenuated when either the pi -or tau-nitrogen of the imidazole side chains of His were methylated, thereby inhibiting formation of the His bridge. Toxicity did not correlate… CONTINUE READING