Alpha-Synuclein Dopaminylation Presented in Plasma of Both Healthy Subjects and Parkinson's Disease Patients

Purpose Alpha-synuclein (alpha-syn) dopaminylation can lead to the death of dopaminergic neurons in the brain and is a risk factor of Parkinson's disease (PD). This study aims to examine whether such a posttranslational modification (PTM) is presented in human blood plasma. Experimental Design In vitro reaction simulation between alpha-syn and dopamine (DA) is conducted to study the biochemical mechanism. Then alpha-syn from human blood plasma samples is detected by using immunoprecipitation-mass spectrometry (IP-MS). Lastly the levels of endogenous alpha-syn and alpha-syn dopaminylation in 88 blood plasma samples from patients with PD, major depressive disorder (MDD), and healthy control (HC) are compared. Results DA modifies alpha-syn with the addition of dopamine-quinone (DAQ) into lysine sites of alpha-syn in vitro and the addition of DAQ and 3,4-dihydroxyphenylacetaldehyde (DOPAL) in plasma samples. The unmodified alpha-syn between the PD and HC groups showed similar levels. The levels of two peptides, one with lysine 34 (K-34) DAQ modification and the other with lysine 23 (K-23) ubiquitination, are significantly higher in PD and MDD compared with HC. Conclusions and Clinical Relevance Thus, alpha-syn dopaminylation is measurable and might be used to indicatethe presence and progression of neurological disorders.