Role of Protein Damage Inflicted by Dopamine Metabolites in Parkinson's Disease: Evidence, Tools, and Outlook

Dopamine is an important neurotransmitter that plays a critical role in motivational salience and motor coordination. However, dysregulated dopamine metabolism can result in the formation of reactive electrophilic metabolites which generate covalent adducts with proteins. Such protein damage can impair native protein function and lead to neurotoxicity, ultimately contributing to Parkinson's disease etiology. In this Review, the role of dopamine-induced protein damage in Parkinson's disease is discussed, highlighting the novel chemical tools utilized to drive this effort forward. Continued innovation of methodologies which enable detection, quantification, and functional response elucidation of dopamine-derived protein adducts is critical for advancing this field. Work in this area improves foundational knowledge of the molecular mechanisms that contribute to dopamine-mediated Parkinson's disease progression, potentially assisting with future development of therapeutic interventions.