The Role of Non-Coding RNAs in the Pathogenesis of Parkinson's Disease: Recent Advancement

Abstract

Parkinson's disease (PD) is a prevalent neurodegenerative aging disorder that manifests as motor and non-motor symptoms, and its etiopathogenesis is influenced by non-coding RNAs (ncRNAs). Signal pathway and gene sequence studies have proposed that alteration of ncRNAs is relevant to the occurrence and development of PD. Furthermore, many studies on brain tissues and body fluids from patients with PD indicate that variations in ncRNAs and their target genes could trigger or exacerbate neurodegenerative pathogenesis and serve as potential non-invasive biomarkers of PD. Numerous ncRNAs have been considered regulators of apoptosis, α-syn misfolding and aggregation, mitochondrial dysfunction, autophagy, and neuroinflammation in PD etiology, and evidence is mounting for the determination of the role of competing endogenous RNA (ceRNA) mechanisms in disease development. In this review, we discuss the current knowledge regarding the regulation and function of ncRNAs as well as ceRNA networks in PD pathogenesis, focusing on microRNAs, long ncRNAs, and circular RNAs to increase the understanding of the disease and propose potential target identification and treatment in the early stages of PD.

Keywords: Parkinson’s disease; dopaminergic neurons; microglia; neuroinflammation; non-coding RNAs.

Figure 1

The self-propelled deterioration cycle in PD. Microglia are active under the pathogenic conditions of PD and release anti-inflammatory cytokines to heal the tissues, saving neurons from apoptosis or death. Continuous stimulation of pathogenic factors, on the other hand, increases the number of toxic phenotypes of microglia, resulting in the release of a significant number of inflammatory cytokines such TNF-, IL-1, iNOS, and IL-6, all of which lead to neuronal damage. Furthermore, damaged or dead DA neurons can directly activate microglia, resulting in an increase in reactive oxygen species (ROS) and pro-inflammatory cytokines. Microglia activation and DA neuronal injury thus form a self-propelled degeneration cycle in PD.

Figure 2

LncRNA representative signal pathways involved in Parkinson’s disease pathogenesis and neuroinflammation. Straight arrows indicate lncRNAs regulate gene (protein) expression in PD pathogenesis. Two consecutive arrows mean that there may be other participants in the process.

Figure 3

The targeted regulation mechanism of miRNA and competitive endogenous RNAs (ceRNAs). (A) The regulation function of miRNAs is to target mRNA molecules with complementary sequences. As a result, the genes can be silenced by cleavage of the mRNA strand. (B) LncRNA and circRNA combine with miRNA so that mRNAs are protected from degradation and consequently translate to proteins.

Figure 4

miRNA representative signal pathways involved in Parkinson’s disease pathogenesis. Straight arrows indicate miRNAs regulate gene (protein) expression in PD pathogenesis. Two consecutive arrows mean that there may be other participants in the process.

Figure 5

miRNA representative signal pathways involved in Parkinson’s disease neuroinflammation. Straight arrows indicate miRNAs regulate gene (protein) expression in PD neuroinflammation. Two consecutive arrows mean that there may be other participants in the process.

Figure 6

ceRNA representative signal pathways involved in Parkinson’s disease pathogenesis. Straight arrows indicate ceRNAs regulate gene (protein) expression in PD pathogenesis. Two consecutive arrows mean that there may be other participants in the process.