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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.
SUBMITTER: Gupta AK
PROVIDER: S-EPMC6488160 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
Gupta Ashish Kumar AK Kumar Gaurav Khunger GK Rani Komal K Pokhriyal Ruchika R Khan Mohd Imran MI Kumar Domada Ratna DR Goyal Vinay V Tripathi Manjari M Gupta Rishab R Chadda Rakesh Kumar RK Vanamail Perumal P Mohanty Ashok Kumar AK Hariprasad Gururao G
Neuropsychiatric disease and treatment 20190424
<h4>Objectives</h4>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 ...[more]