Copper catalysed oxidation of amino acids and Alzheimer's disease

Metal-catalyzed oxidation (MCO) can lead to damage of bio-molecules and is implicated in neurodegenerative diseases, such as Alzheimer's disease (AD). The amino acid residues, tyrosine, histidine and methionine, have been proposed to play important roles in metal mediated oxidative stress and subsequent reactions of amyloid β peptide (Aβ) a major contributor in the pathogenesis of AD. The MCO of Aβ residues, particularly histidine, methionine and tyrosine, are reviewed. MCO of Aβ histidine and tyrosine residues can facilitate oligomerization and may play a role in both amyloid formation and Aβ neurotoxicity. Further work is needed to determine the importance of Aβ oxidation in AD and the role of Aβ oxidation products and oxidative stress in disease progression. The mechanisms of Aβ MCO are complex and multiple reaction products can form. Further study is needed to determine the mechanisms by which Aβ MCO occurs in vivo. In addition, new analytical methods are required to monitor the formation of Aβ MCO products formed during AD. The copper-H 2 O 2 redox system provides a chemical model by which Aβ MCO can be studied in vitro and can be used to produce oxidatively modified amino acid residues for use as standards in developing new analytical methods to monitor Aβ MCO. © 2004 Kluwer Academic Publishers.