Downregulation of miR-124 in MPTP-treated mouse model of Parkinson’s disease and MPP iodide-treated MN9D cells modulates the expression of the calpain/cdk5 pathway proteins.
Abstract
Parkinson's disease (PD) is a debilitating neurodegenerative disorder causing severe motor disabilities resulting from the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) region of the midbrain. MicroRNAs (miRNAs) are small, non-coding RNAs which play a major role in several cellular processes in health and disease by regulating gene expression post-transcriptionally. Aberrant miRNA expression has been detected in post-mortem human PD brain samples, in vitro and in vivo PD models. However, none of the studies have focused on the role of the brain-abundant miR-124 in PD. In this study, we have evaluated the expression changes of miR-124 in the SN of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. MiRNA expression analysis by qPCR revealed a decrease in the expression of brain-enriched miR-124 in the SN of MPTP-treated mice as compared to controls. Further, in vitro study revealed a decrease in the expression of miR-124 in MN9D dopaminergic neurons treated with methyl phenyl pyridinium (MPP) iodide. The expression of calpains 1 and 2 which is modulated by miR-124 was increased in the SNc of MPTP-treated mice as observed at different time points after treatment and in the MN9D dopaminergic neurons treated with MPP iodide leading to increased expression of the p35 cleavage product, p25 and cyclin-dependent kinase 5 (cdk5). Calpain-p25-mediated increase in cdk5 expression leading to dopaminergic neuronal death has been demon…
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Altered expression of miR-124 is associated with multiple neuroinflammatory disorders such as Parkinson's, Alzheimer's, and Huntington's disease.
“Notably, altered expression of miR-124 has been associated with multiple neuroinflammatory disorders such as Parkinson’s (Kanagaraj et al., 2014; Wang et al., 2016; Dong et al., 2018; Yao et al., 2018, 2019), Alzheimer’s Diseases (Lukiw, 2007; Smith et al., 2011; Fang et al., 2012; Zhou et al., 2018), and Huntington’s disease (Johnson and Buckley, 2009).”
From Engineered Extracellular Vesicles Loaded With miR-124 Attenuate Cocaine-Mediated Activation of Microglia (2020) · cites this paper as Kanagaraj et al., 2014
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Skalsky, R. L., & Cullen, B. R. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024248 · Cited by 170 · see citing works
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MicroRNA-124 loaded nanoparticles enhance brain repair in Parkinson's disease
Saraiva, C., Paiva, J., Santos, T., Ferreira, L., & Bernardino, L. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.06.005 · Cited by 169 · see citing works
Chivero, E. T., Liao, K., Niu, F., Tripathi, A., Tian, C., Buch, S., & Hu, G. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00573 · Cited by 69 · see citing works
MicroRNA-124: A Key Player in Microglia-Mediated Inflammation in Neurological Diseases
Zhao, J., He, Z., & Wang, J. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.771898 · Cited by 66 · see citing works
miR-124: A Promising Therapeutic Target for Central Nervous System Injuries and Diseases
Xu, J., Zheng, Y., Wang, L., Liu, Y., Wang, X., Li, Y., & Chi, G. (2022) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-021-01091-6 · Cited by 55 · see citing works
- Authors
- Kanagaraj, N., Beiping, H., Dheen, S. T., & Tay, S. S. W.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 272
- Pages
- 167-179
- ISSN
- 0306-4522
- Cited by
- 119
- References
- 1
- Language
- en
- Funders
- Ministry of Education - Singapore
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