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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

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...

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Autores principales: Gupta, Ashish Kumar, Pokhriyal, Ruchika, Khan, Mohd Imran, Kumar, Domada Ratna, Gupta, Rishab, Chadda, Rakesh Kumar, Ramachandran, Rashmi, Goyal, Vinay, Tripathi, Manjari, Hariprasad, Gururao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781638/
https://www.ncbi.nlm.nih.gov/pubmed/31632033
http://dx.doi.org/10.2147/NDT.S214217
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author Gupta, Ashish Kumar
Pokhriyal, Ruchika
Khan, Mohd Imran
Kumar, Domada Ratna
Gupta, Rishab
Chadda, Rakesh Kumar
Ramachandran, Rashmi
Goyal, Vinay
Tripathi, Manjari
Hariprasad, Gururao
author_facet Gupta, Ashish Kumar
Pokhriyal, Ruchika
Khan, Mohd Imran
Kumar, Domada Ratna
Gupta, Rishab
Chadda, Rakesh Kumar
Ramachandran, Rashmi
Goyal, Vinay
Tripathi, Manjari
Hariprasad, Gururao
author_sort Gupta, Ashish Kumar
collection PubMed
description 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 spectrometric 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 dopamine-dictated clinical scenarios. α-2 Macroglobulin is a potential biomarker to monitor pharmacological therapy in Parkinson’s disease and schizophrenia.
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spelling pubmed-67816382019-10-18 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 Gupta, Ashish Kumar Pokhriyal, Ruchika Khan, Mohd Imran Kumar, Domada Ratna Gupta, Rishab Chadda, Rakesh Kumar Ramachandran, Rashmi Goyal, Vinay Tripathi, Manjari Hariprasad, Gururao Neuropsychiatr Dis Treat Original Research 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 spectrometric 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 dopamine-dictated clinical scenarios. α-2 Macroglobulin is a potential biomarker to monitor pharmacological therapy in Parkinson’s disease and schizophrenia. Dove 2019-10-02 /pmc/articles/PMC6781638/ /pubmed/31632033 http://dx.doi.org/10.2147/NDT.S214217 Text en © 2019 Gupta et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Gupta, Ashish Kumar
Pokhriyal, Ruchika
Khan, Mohd Imran
Kumar, Domada Ratna
Gupta, Rishab
Chadda, Rakesh Kumar
Ramachandran, Rashmi
Goyal, Vinay
Tripathi, Manjari
Hariprasad, Gururao
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781638/
https://www.ncbi.nlm.nih.gov/pubmed/31632033
http://dx.doi.org/10.2147/NDT.S214217
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