Abstract
Parkinson’s disease (PD) is a severely debilitating neurodegenerative disease, affecting the motor system, leading to resting tremor, cogwheel rigidity, bradykinesia, walking and gait difficulties, and postural instability. The severe loss of dopaminergic neurons in the substantia nigra pars compacta causes striatal dopamine deficiency and the presence of Lewy bodies indicates a pathological hallmark of PD. Although the current treatment of PD aims to preserve dopaminergic neurons or to replace dopamine depletion in the brain, it is notable that complete recovery from the disease is yet to be achieved. Given the complexity and multisystem effects of PD, the underlying mechanisms of PD pathogenesis are yet to be elucidated. The advancement of medical technologies has given some insights in understanding the mechanism and potential treatment of PD with a special interest in the role of microRNAs (miRNAs) to unravel the pathophysiology of PD. In PD patients, it was found that striatal brain tissue and dopaminergic neurons from the substantia nigra demonstrated dysregulated miRNAs expression profiles. Hence, dysregulation of miRNAs may contribute to the pathogenesis of PD through modulation of PD-associated gene and protein expression. This review will discuss recent findings on PD-associated miRNAs dysregulation, from the regulation of PD-associated genes, dopaminergic neuron survival, α-synuclein-induced inflammation and circulating miRNAs. The next section of this review also provides an update on the potential uses of miRNAs as diagnostic biomarkers and therapeutic tools for PD.
Highlights
Expression compared to controlBCL-2 protein and in-activation of pro-apoptotic caspase-3 (Fragkouli and Doxakis, 2014)
Yong Hui Nies1, Nor Haliza Mohamad Najib1, Wei Ling Lim2, Mohd Amir Kamaruzzaman1, Mohamad Fairuz Yahaya1 and Seong Lin Teoh1*
Compelling evidences relating to the multisystem effects of Parkinson’s disease (PD) reported that the primary feature defects in movement control are caused by the death of DA neurons within the substantia nigra pars compacta (SNpc) (Chen et al, 2019)
Summary
BCL-2 protein and in-activation of pro-apoptotic caspase-3 (Fragkouli and Doxakis, 2014) Another miRNA targeting SNCA, miR-203a-3p expression was down-regulated in MMP+-treated human dopaminergic neuroblastoma, SH-SY5Y cells (Jiang et al, 2020). Down-regulation of miR-146a expression led to the inhibition of NF-κβ phosphorylation and increased Parkin level in the rotenone-treated SH-SY5Y cells (Jauhari et al, 2020). The up-regulation of miR-4639-5p led to the down-regulation of DJ-1 protein level resulted in severe oxidative stress and neuronal death in MPP+- and rotenone-treated SH-SY5Y cells (Chen et al, 2017). MiR-145-3p and miR-874 are among other miRNAs that were predicted to regulate DJ-1 expression, and both were shown to be highly expressed in the saliva of PD patients (Chen et al, 2020)
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