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Ashish Kumar Gupta,1,* Ruchika Pokhriyal,1,* Mohd Imran Khan,1 Domada Ratna Kumar,1 Rishab Gupta,2 Rakesh Kumar Chadda,2 Rashmi Ramachandran,3 Vinay Goyal,4 Manjari Tripathi,4 Gururao Hariprasad1 1Department of Biophysics; 2Department of Psychiatry; 3Department of Anaesthesia; 4Department of Neurology, All India Institute of Medical Sciences, New Delhi 110029, India*These authors contributed equally to this workCorrespondence: Gururao HariprasadDepartment of Biophysics, All India Institute of Medical Sciences, Ansari nagar, New Delhi 110029, IndiaTel +91 11 26594029Fax +91 11 26588663Email g.hariprasad@rediffmail.comAim: 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.Keywords: Parkinson’s disease, schizophrenia, iTRAQ proteomics, dopamine, biomarkers, therapeutic efficacy, alpha-2-macroglobulin

Ashish Kumar Gupta,1 Ruchika Pokhriyal,1 Uddipan Das,1 Mohd Imran Khan,1 Domada Ratna Kumar,1 Rishab Gupta,2 Rakesh Kumar Chadda,2 Rashmi Ramachandran,3 Vinay Goyal,4 Manjari Tripathi,4 Gururao Hariprasad11Department of Biophysics; 2Department of Psychiatry; 3Department of Anaesthesia; 4Department of Neurology, All India Institute of Medical Sciences, New Delhi 110029, IndiaBackground and objective: Dopamine plays an important role in the disease pathology of Parkinson’s disease and schizophrenia. These two neuropsychiatric disorders represent disease end points of the dopaminergic spectrum where Parkinson’s disease represents dopamine deficit and schizophrenia represents dopamine hyperactivity in the mid-brain. Therefore, current treatment strategies aim to restore normal dopamine levels. However, during treatment patients develop adverse effects due to overshooting of physiological levels of dopamine leading to psychosis in Parkinson’s disease, and extrapyramidal symptoms in schizophrenia. Absence of any laboratory tests hampers modulation of pharmacotherapy. Apolipoprotein E and α-synuclein have an important role in the neuropathology of these two diseases. The objective of this study was to evaluate cerebrospinal fluid (CSF) concentrations of apolipoprotein E and α-synuclein in patients with these two diseases so that they may serve as biomarkers to monitor therapy in Parkinson’s disease and schizophrenia.Methods: Drug-naïve Parkinson’s disease patients and Parkinson’s disease patients treated with dopaminergic therapy, neurological controls, schizophrenic patients treated with antidopaminergic therapy, and drug-naïve schizophrenic patients were recruited for the study and CSF was collected. Enzyme-linked immunosorbent assays were carried out to estimate the concentrations of apolipoprotein E and α-synuclein. Pathway analysis was done to establish a possible role of these two proteins in various pathways in these two dopamine dictated diseases.Results: Apolipoprotein E and α-synuclein CSF concentrations have an inverse correlation along the entire dopaminergic clinical spectrum. Pathway analysis convincingly establishes a plausible hypothesis for their co-regulation in the pathogenesis of Parkinson’s disease and schizophrenia. Each protein by itself or as a combination has encouraging sensitivity and specificity values of more than 55%.Conclusion: The dynamic variation of these two proteins along the spectrum is ideal for them to be pursued as pharmacotherapeutic biomarkers in CSF to monitor pharmacological efficacy in Parkinson’s disease and schizophrenia.Keywords: cerebrospinal fluid, Parkinson’s disease, schizophrenia, dopamine, apolipoprotein E, α-synuclein, biomarkers, treatment monitoring

Baluta is the first Dalit autobiography written by Daya Pawar, published in 1978. Originally written in Marathi and took a long time of about two scores to be translated into English in 2015 by Jerry Pinto. The depiction of the writer’s personal life, feeling, and encounters with upper-class people is bitter and heart-wrenching. The self-revelation of the author has stupefied and made dumb stricken those who have gone through his autobiography. The book is an account of the clinical reality of people living in squalor, poverty, and sordid dirtiness of the unhygienic ambience of brothel, gambling and pub-houses. There are many sorts of characters ensuring the variety and giving a glimpse of Chaucer’s The Canterbury Tales.