Transformation of beta-amyloid (A beta) (1-42) tyrosine to L-Dopa as the result of in vitro hydroxyl radical attack

A form of beta-amyloid peptide A beta ending at amino acid 42 (A beta 42) i s the major component of senile amyloid plaques in Alzheimer's Disease (AD) . The A beta-peptide earliest modifications are extremely important since t hey constitute the key events in the progression towards further changes fi nally leading to fibril formation and to A beta deposits which constitute t he core pathological change in AD. Chemical and conformational early modifi cations of the beta-amyloid peptide are critical steps in AD pathogenesis a nd have been widely investigated. We now show that a Fenton-type OH-generat ing system is capable of generating L-Dopa (3,4-dihydroxyphenylalanine) in the tyrosine residue of A beta-peptide via aromatic ring hydroxylation, as the result of hydroxyl radical attack on proteins. Since L-Dopa is not a co nstituent of mammalian proteins and peptides, the formation of L-Dopa in A beta in vitro constitutes a possible important modification caused by hydro xyl radical attack. These results lay the groundwork for further studies on modification and damage associated with the degenerative disorder in AD wh ere oxidative stress and inflammation are known to occur.