Abstract
Parkinson’s disease (PD) is the age-related neurological disorder characterized by the degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc). PD is based on motor deficits which start to appear when up to 80% of the DA neurons of SNpc have been lost. Effective management of PD requires the development of novel biomarkers. Therefore, the present study aimed to characterize biomarkers of PD using miRNomics, proteomics, and bioinformatics approaches. Rats exposed to rotenone (2.5 mg/kg b.wt) for 2 months were used as an animal model to identify the unbiased set of miRNAs and proteins deregulated in blood samples. OpenArray, a real-time PCR-based array, is used for high-throughput profiling of miRNAs, and liquid chromatography–tandem mass spectrometry (LC–MS/MS) was used to carry out the global protein profiling. Systematic bioinformatics analysis of miRNAs and proteins was also performed, including annotation, functional classification and functional enrichment, network analysis, and miRNA–protein interaction analysis. Expression of 19 miRNAs and 96 proteins was significantly upregulated in the blood, while 22 proteins were significantly downregulated in blood samples of rotenone-exposed rats. In silico pathway analysis of deregulated proteins and miRNAs in rotenone-exposed rats has identified multiple pathways leading to PD. In summary, we have identified a set of miRNAs (miR-144, miR-96, and miR-29a) and proteins (PLP1, TUBB4A, and TUBA1C), which can be used as a potential biomarker of PD, while further validation required large human population studies.
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All data generated or analyzed during this study are included in this article (and its supplementary information files).
Code Availability
NCBI-GEO accession number, GSE180996, and CCMS-MassIVE accession number, MSV000087910.
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Acknowledgements
Mr. Sanjeev Kumar Yadav is grateful to CSIR, New Delhi, for providing JRF/SRF fellowship. The technical support provided by the IITR — central instrumental (HPLC-ECD) facility for the quantification of neurotransmitters, is also acknowledged. The CSIR-IITR communication reference number is IITR/SEC/2021-2022/22.
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The funding of the present study has been provided by the Science and Engineering Research Board (SERB), New Delhi (Grant Sanction no. EMR/2016/002965).
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Sanjay Yadav and Devendra Parmar have planned the study and monitored it throughout and prepared the final draft of the manuscript. Sanjay Yadav has guided the students in the development of protocols and new methods. Sanjeev Kumar Yadav performed all the OpenArray and proteomics experiments and data analysis and prepared the first draft of the manuscript. Anuj Pandey helped in the animal dosing experiments. Sana Sarkar helped in the real-time PCR. Smriti Singh Yadav helped in the sample processing.
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All the animal experiments were approved by the Institutional Animal Ethics Committee (IAEC), CSIR—Indian Institute of Toxicology Research, Lucknow, India. The approved reference number was IITR/IAEC/08/17–36/2018.
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Yadav, S.K., Pandey, A., Sarkar, S. et al. Identification of Altered Blood MicroRNAs and Plasma Proteins in a Rat Model of Parkinson’s Disease. Mol Neurobiol 59, 1781–1798 (2022). https://doi.org/10.1007/s12035-021-02636-y
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DOI: https://doi.org/10.1007/s12035-021-02636-y