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

脑脊液蛋白质组学用于鉴定 α2-巨球蛋白作为潜在生物标记物,用于监测帕金森病和精神分裂症多巴胺指示疾病状态的药物治疗效果

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作者:Ashish Kumar Gupta #, Ruchika Pokhriyal #, Mohd Imran Khan, Domada Ratna Kumar, Rishab Gupta, Rakesh Kumar Chadda, Rashmi Ramachandran, Vinay Goyal, Manjari Tripathi, Gururao Hariprasad

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

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.

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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