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

Abstract

Purpose: Alpha-synuclein (α-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 α-syn and dopamine (DA) is conducted to study the biochemical mechanism. Then α-syn from human blood plasma samples is detected by using immunoprecipitation-mass spectrometry (IP-MS). Lastly the levels of endogenous α-syn and α-syn dopaminylation in 88 blood plasma samples from patients with PD, major depressive disorder (MDD), and healthy control (HC) are compared.

Results: DA modifies α-syn with the addition of dopamine-quinone (DAQ) into lysine sites of α-syn in vitro and the addition of DAQ and 3,4-dihydroxyphenylacetaldehyde (DOPAL) in plasma samples. The unmodified α-syn between the PD and HC groups showed similar levels. The levels of two peptides, one with lysine 34 (³⁴ K) DAQ modification and the other with lysine 23 (²³ K) ubiquitination, are significantly higher in PD and MDD compared with HC.

Conclusions and clinical relevance: Thus, α-syn dopaminylation is measurable and might be used to indicatethe presence and progression of neurological disorders.

Keywords: Parkinson's disease; alpha-synuclein; dopamine; plasma.