Abstract
BackgroundThere have been a number of reports implicating the association of microRNAs (miRs) and the MAPK signaling pathway with the dopaminergic neuron, which is involved in the development of Parkinson’s disease (PD). The present study was conducted with aims of exploring the role of miR-96 in the activation of iNOS and apoptosis of dopaminergic neuron through the MAPK signaling pathway in mice with PD.MethodsThe miR and the differentially expressed gene in PD were screened out and the relationship between them was verified. A mouse model of PD induced by MPTP and was then constructed and treated with miR-96 mimic/inhibitor and CACNG5 overexpression plasmid to extract nigral dopaminergic neuron for the purpose of detecting the effect of miR-96 on PD. The TH and iNOS positive neuronal cells, the apoptotic neuronal cells by TUNEL staining, and expression of miR-96, CACNG5, iNOS, p38MAPK, p-p38MAPK, c-Fos, Bax, and Bcl-2 in substantia nigra dopaminergic neuronal tissues were evaluated.ResultsThe results obtained from the aforementioned procedure were then verified by cell culture of the SH-SY5Y cells, followed by treatment with miR-96 mimic/inhibitor, CACNG5 overexpression plasmid and the inhibitor of the MAPK signaling pathway. CACNG5 was confirmed as a target gene of miR-96. The inhibition of miR-96 resulted in a substantial increase in nigral cells, TH positive cells and expression of CACNG5 and Bcl-2 in nigral dopaminergic neuronal tissues, and a decrease in iNOS positive cells, apoptotic neuronal cells, and expression of iNOS, p38MAPK, p-p38MAPK, c-Fos, and Bax.ConclusionThe above results implicated that the downregulation of miR-96 inhibits the activation of iNOS and apoptosis of dopaminergic neuron through the blockade of the MAPK signaling pathway by promoting CACNG5 in mice with PD.
Highlights
There have been a number of reports implicating the association of microRNAs and the mitogen-activated protein kinases (MAPK) signaling pathway with the dopaminergic neuron, which is involved in the development of Parkinson’s disease (PD)
Calcium voltage-gated channel auxiliary subunit gamma 5 (CACNG5) was confirmed as a target gene of miR-96 and a potential regulator of the MAPK signaling pathway Based on the results from an online prediction website used to detect the relationship among miR-96, CACNG5 and the MAPK signaling pathway, a binding site was found to exist between miR-96 and CACNG5, as a result of which CACNG5 was identified as a target gene of miR-96
The levels of CACNG5 were elevated so that the expression of Inducible nitric oxide synthase (iNOS), the downstream molecule of MAPK was inhibited and this was done for the purpose of demonstrating that CACNG5 mediates the regulation of MAPK signaling pathway through miR-96 (Fig. 2c)
Summary
There have been a number of reports implicating the association of microRNAs (miRs) and the MAPK signaling pathway with the dopaminergic neuron, which is involved in the development of Parkinson’s disease (PD). Parkinson’s disease (PD) is a major neurodegenerative movement disorder affecting over 1% old people over 60 years old (Crabtree and Zhang 2012). It is the second most commonly occurring type of neurodegenerative disease following Alzheimer’s disease with a lifetime risk of 4–5% (Mullin and Schapira 2013). Midbrain dopaminergic neurons play an essential regulatory role in several brain functions, including emotion, cognition and voluntary movements (Villaescusa et al 2016). MicroRNAs (miRNAs) have been found to play a key role in the function, and development of the nervous system as well as the pathogenesis of several diseases of the nervous system, and they have been used as a therapeutic agent in PD (Harraz et al 2011)
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