Abstract
BackgroundParkinson's disease (PD) is a neurodegenerative disorder which mainly affects the elderly population of various societies. The main hallmark of this disease is the loss of dopaminergic (DA) neurons. So far, numerous studies have implied the role of microRNAs in fine‐tuning cellular processes including apoptosis. Studies have also shown that miR‐34a is mainly involved in age‐related disorders including Alzheimer's disease, and its expression is usually higher in the brain sample patients. Furthermore, the key role of miR‐34a in the expression of BCL‐2, and thus, in vitro and in vivo apoptosis has been revealed. miR‐34a/BCL‐2 axis is therefore of critical importance in inducing or inhibiting apoptosis.MethodsIn this study, human SH‐SY5Y cells were treated with MPP+ and the expression of miR‐34a and BCL2 was assessed.ResultsOur results also showed that treating human SH‐SY5Y neuronal cells using MPP+ to induce oxidative stress and apoptosis led to the upregulation of miR‐34a, as compared to the nontreated control group. Moreover, evaluating the expression level of BCL‐2 in these cells indicated a contradictory pattern, as compared with miR‐34a. It was also revealed that the expression of BCL‐2 was significantly decreased in MPP+‐treated cells, thereby confirming previous studies regarding a new concept. In this study, we show that miR‐34a/BCL‐2 axis is directly correlated with oxidative stress and apoptosis in SH‐SY5Y cells as a model of DA neurons.ConclusionmiR‐34a and its target gene, BCL‐2, play a possible role in the induction of apoptosis in DA neurons, and therefore, they have a potential role in the pathogenesis of PD. Consequently, the therapeutic potential of miR‐34a could be considered in order to inhibit the progression of PD.
Highlights
Parkinson's disease (PD) is a progressive neurodegenerative disease of CNS and the second most common neurodegenerative disorder (De Rijk et al, 2000)
SH‐SY5Y cells were seeded at a density of 8 × 105 in plates and treated with a concentration of 2,000 μM of MPP+ in order to evaluate the expression of miR‐34a and its target gene, BCL‐2
Several studies have shown that miRNAs are abundantly found in brain; any modifications in the brain miRNA network may contribute to the development of Results are normalized relative to GAPDH expression (*indicates p < 0.05, and ***is representing p < 0.001, relative to the control)
Summary
Parkinson's disease (PD) is a progressive neurodegenerative disease of CNS and the second most common neurodegenerative disorder (De Rijk et al, 2000). DA neurons located in SNc send their projections to the dorsal striatum, which mainly regulates controlled movements, emotions, and complex behaviors Progressive degeneration of these neural cells in human brains leads to motor symptoms in PD (Harraz, Dawson, & Dawson, 2011). Recent studies on the miRNA profiling of PD patients brain samples have determined the downregulation of miR‐34b and miR‐34c in different brain regions including substantia nigra and amygdala (Miñones‐Moyano et al, 2011). It is not specified whether the downregulation of these miRNAs is by virtue of DA neurons degeneration or their decrease in the surviving neurons. The aim of this study was to suggest miR‐34a and one of its target genes, BCL‐2, as some novel miRNA‐gene axis involved in the DA neurons cell death and as a possible cause of pathogenesis in PD
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