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Role of microRNA‐9 in the pathogenesis of Parkinson's Disease
Author(s) -
Goh Suh Yee,
Yeo Xin Yi,
Srinivasan Dinesh Kumar,
Dheen S Thameem,
Tay Samuel Sam Wah
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.545.6
Subject(s) - pars compacta , mptp , substantia nigra , neurodegeneration , downregulation and upregulation , parkinson's disease , pathogenesis , microvesicles , neurogenesis , microrna , neuroprotection , microglia , regulator , microbiology and biotechnology , population , biology , chemistry , neuroscience , disease , medicine , immunology , biochemistry , inflammation , gene , environmental health
Parkinson's disease (PD) is the second most prevalent neurodegenerative disease in the aging population. Previously, our lab has shown that miR‐9 is upregulated in the substantia nigra pars compacta (SNc) in pre‐clinical models of PD [1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated mice]. Briggs et al (2015) has also reported this trend in the SNc of post‐mortem PD patients. miRNAs are post‐transcriptional regulators of gene expression that are involved in the maintenance of normal cellular functions. While miR‐9 is well‐studied as a regulator of neurogenesis during brain development, its upregulation observed in PD suggests that miR‐9 may have other functions that contributes to PD pathogenesis. In this study, we are interested to investigate the miR‐9‐mediated mechanisms involved in the development of PD. Using miRNA qPCR, we verified the increase in miR‐9 levels in in vitro PD models [MN9D and SH‐SY5Y neuronal cells treated with 1‐methyl‐4‐phenylpyridinium (MPP) iodide]. MPP treatment decreased neuronal cell viability by about 30% and the inhibition of miR‐9 significantly reversed this trend, suggesting that miR‐9 plays a role in neurodegeneration. In addition, using NanoSight technology, we discovered a significant increase in the concentration and size of exosomes released by neuronal cells treated with MPP iodide. Interestingly, these exosomes also contained higher miR‐9 levels as compared to exosomes released by neurons under control conditions. This suggests that miR‐9 may be transported to other cell types (such as microglia) to regulate other events in PD, for instance, neuroinflammation. These research findings implicate miR‐9 as a potential diagnostic biomarker as well as a potential therapeutic target for PD treatment. Support or Funding Information This work was supported by a research grant from the Singapore Ministry of Education Academic Research Fund Tier 1. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .