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MiR-193b deregulation is associated with Parkinson's disease |
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| Authors: | Masoud Baghi Elaheh Yadegari Mahsa Rostamian Delavar Maryam Peymani Mazdak Ganjalikhani-Hakemi Mehri Salari Mohammad Hossein Nasr-Esfahani Timothy L. Megraw Kamran Ghaedi |
| Affiliation: | 1. Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran Contribution: Formal analysis (equal), Investigation (equal), Methodology (equal), Project administration (equal), Resources (equal), Software (equal), Writing - original draft (equal), Writing - review & editing (equal);2. Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran Contribution: Formal analysis (equal), Investigation (equal), Methodology (equal), Resources (equal), Software (equal), Writing - original draft (equal);3. Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran Contribution: Formal analysis (equal), Investigation (equal), Methodology (equal), Project administration (equal), Validation (equal), Writing - original draft (equal), Writing - review & editing (equal);4. Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran Contribution: Investigation (equal);5. Immunology Department, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Contribution: Formal analysis (equal), Resources (equal), Supervision (equal);6. Functional Neurosurgery Research Center, Shohada Tajrish Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran Contribution: Resources (equal), Supervision (equal), Validation (equal);7. Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran;8. Department of Biomedical Sciences, Florida State University, College of Medicine, Tallahassee, FL, USA;9. Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran |
| Abstract: | PGC-1α/FNDC5/BDNF has found to be a critical pathway in neurodegeneration. MicroRNAs (miR(NA)s) are non-coding regulatory RNAs whose dysregulation has been observed in multiple neurological disorders, and miRNA-mediated gene deregulation plays a decisive role in PD. Here, candidate miRNA was chosen based on the literature survey and in silico studies. Chronic and acute models of PD were created using MPP+-treated SH-SY5Y cells. Twenty PD patients and 20 healthy volunteers were recruited. RT-qPCR was performed to assess the expression of miRNA and genes. Severe mitochondrial dysfunction induced by acute MPP+ treatment instigated compensatory mechanisms through enhancing expression of PGC-1α/FNDC5/BDNF pathway genes, while chronic MPP+ toxicity led to down-regulated levels of the genes in SH-SY5Y cells. PD peripheral blood mononuclear cells (PBMCs) also showed decreased expression of target genes. There were significant changes in the level of miR-193b in both models, as well as PD PBMCs. Moreover, miR-193b overexpression significantly affected PGC-1α, FNDC5 and TFAM levels. Interestingly, down-regulations of PGC-1α, FNDC5, BDNF and TFAM were inversely correlated with miR-193b up-regulation in PD PBMCs. This study showed the deregulation of PGC-1α/FNDC5/BDNF pathway in PD models and PBMCs, verifying its importance in neurodegeneration. Our findings also revealed that miR-193b functions in PD development, possibly through regulating PGC-1α/FNDC5/BDNF pathway, suggesting miR-193b as a potential biomarker for PD diagnosis. |
| Keywords: | miR-193b MPP+ Parkinson's disease peripheral blood mononuclear cells PGC-1α/FNDC5/BDNF pathway SH-SY5Y cells |