Cerebrospinal fluid proteomics for identification of α2-macroglobulin as a potential biomarker to monitor pharmacological therapeutic efficacy in dopamine dictated disease states of Parkinson’s disease and schizophrenia

Abstract

Aim: Parkinson’s disease and schizophrenia are clinical end points of dopaminergic deficit and excess, respectively, in the mid-brain. In accordance, current pharmacological interventions aim to restore normal dopamine levels, the overshooting of which culminates in adverse effects which results in psychotic symptoms in Parkinson’s disease and extra-pyramidal symptoms in schizophrenia. Currently, there are no laboratory assays to assist treatment decisions or help foresee these drug side-effect outcomes. Therefore, the aim was to discover a protein biomarker that had a varying linear expression across the clinical dopaminergic spectrum. Materials and methods: iTRAQ-based proteomic experiments along with mass spectro-metric analysis was used for comparative proteomics using cerebrospinal fluid (CSF). CSF fluid was collected from 36 patients with Parkinson’s disease, 15 patients with urological diseases that served as neurological controls, and seven schizophrenic patients with hallucinations. Validation included ELISA and pathway analysis to highlight the varying expression and provide plausible molecular pathways for differentially expressed proteins in the three clinical phenotypes. Results: Protein profiles were delineated in CSF from Parkinson’s disease patients, neurological control and schizophrenia, respectively. Ten of the proteins that were identified had a linear relationship across the dopaminergic spectrum. α-2-Macroglobulin showed to be having high statistical significance on inter-group comparison on validation studies using ELISA. Conclusions: Non-gel-based proteomic experiments are an ideal platform to discover potential biomarkers that can be used to monitor pharmaco-therapeutic efficacy in dopa-mine-dictated clinical scenarios. α-2 Macroglobulin is a potential biomarker to monitor pharmacological therapy in Parkinson’s disease and schizophrenia.