<p>2D-DIGE as a strategy to identify serum protein biomarkers to monitor pharmacological efficacy in dopamine-dictated states of Parkinson&rsquo;s disease and schizophrenia</p>

Abstract

Objectives Parkinson’s disease and schizophrenia are clinical scenarios that occur due to dopaminergic deficit and hyperactivity in the midbrain, respectively. Current pharmacological interventions for these two diseases therefore aim to restore normal dopamine levels in the midbrain. But during therapy, there is a overshooting of dopamine concentrations that result in hallucinations in Parkinson’s disease patients and extra-pyramidal symptoms in schizophrenic patients. This causes a lot of inconvenience to the patents and the clinicians. There are no tests currently available to monitor drug efficacy in these two neuropsychiatric diseases. Materials and methods Parkinson’s disease and schizophrenic naïve patients were recruited. Serum proteins isolated from these two clinical phenotypes were labeled with fluorescent cyanine dyes and analyzed by two-dimensional difference in gel electrophoresis proteomic experiment. Differentially expressed spots that had consistent expression pattern across five sets of biological replicate gels were trypsin digested and subjected to mass spectrometric analysis for protein identification. Validation experiments were done for the identified proteins using antibody-based assay on a patient cohort that included naïve, treated, and those who had side effects. Results Serum α- and β-globin chains were identified as differentially expressed proteins having threefold higher expressions in Parkinson’s patients as compared to schizophrenia. Interestingly, concentrations of these two proteins had an inverse correlation across clinical phenotypes in the dopaminergic spectrum. RBC contamination as a source for these proteins was ruled out. Conclusion There is a clear association of free serum globin with dopaminergic clinical states. This lays a platform for protein biomarker–based monitoring of pharmacological efficacy in Parkinson’s disease and schizophrenia.

<p>Evaluation of α-synuclein and apolipoprotein E as potential biomarkers in cerebrospinal fluid to monitor pharmacotherapeutic efficacy in dopamine dictated disease states of Parkinson’s disease and schizophrenia</p>

“…This turnover is a response mechanism to counter the damage at synaptic terminals because of inflammation or oxidative stress, both of which are elevated in Parkinson’s disease 77. In a previous study by our group, the level of alpha-2-macroglobulin was found to be elevated in Parkinson’s disease as compared to schizophrenia 22. Interestingly, LRP is a common receptor for apolipoprotein E, alpha-2-macroglobulin and amyloid precursor protein 78.…”

“…The unavailability of reliable biomarkers to monitor drug therapy in Parkinson’s disease and schizophrenia provides opportunities for clinical proteomic-based biomarker discovery in this field. In the recent past, our group has been dedicatedly involved in protein biomarker discovery to assess treatment in both Parkinson’s disease and schizophrenia 21,22…”