Functional deactivation of cellular proteins by adduct formation with oxidized dopamine has been proposed as a critical step in the degeneration of neurons of the nigrostriatal projection in Parkinson's disease and methamphetamine toxicity. However, the identity of the particular proteins which form adducts is currently not known. We propose to create antibody reagents with affinity for protein-dopamine adducts, and to identify and sequence adsorbed adducts using triple-quadrupole mass spectroscopy. Knowledge of the protein targets should help guide future efforts to protect neurons by means of pharmacological intervention or genetic modification. Also, this effort will expand the application of immunoaffinity-directed mass spectroscopy as a general method for systematic analysis of natural hapten-protein adducts.
