MicroRNA machinery in Parkinson’s disease: a platform for neurodegenerative diseases

Abstract

MicroRNAs (miRNAs) are noncoding RNAs that recognize their protein-coding target genes and whereby subjugate them after transcription. Despite the infancy of this field of science, the role of miRNAs in neurodegeneration is well-acknowledged. This review was conducted to indicate that Parkinson’s disease (PD) is not excluded from this rule. To this end, we evaluated the existing literature and arranged PD-associated miRNAs according to their mechanism of action, particularly apoptosis, autophagy, inflammation, mitochondrial dysfunction and oxidative stress. According to this arrangement, a majority of PD-associated miRNAs were indicated to influence autophagic/apoptotic pathways. We also categorized PD-associated miRNAs according to that they could exert detrimental or beneficial or both into three sets, activator, inhibitor, and double-edged, correspondingly. Considering this criterion, a majority of PD-associated miRNAs were included in the activator category. In addition, evidences from genetic association studies investigating genetic variants of or related to miRNAs in PD patients are presented. Finally, possible applications of the miRNA machinery in PD, including mechanistic networks, diagnostic, prognostic and therapeutic potentials, are discussed. But there may be additional miRNAs involved in the pathogenesis of PD which have hitherto remained unknown and thus further studies are needed to explore the issue and to extend this platform.

Keywords:

• microRNAs
• Parkinson’s disease
• neurodegenerative diseases
• inflammation
• autophagy
• apoptosis
• oxidative stress

Key issues

• The miRNAs involved in the pathophysiological process of Parkinson’s disease (PD) can interfere with an array of molecular pathways, mainly apoptosis, autophagy, inflammation, mitochondrial dysfunction and oxidative stress.

• A majority of PD-related miRNAs are likely to influence autophagic/apoptotic pathways.

• PD-related miRNAs can be categorized according to their mechanism of action into three: activator or inhibitor of dopaminergic degeneration or both of them.

• The activator set comprises miR-21, miR-26b, miR-96-5p, miR-106a, miR-128, miR-132, miR-133b, miR-155, miR-212, miR-224, miR-301b, miR-320a, miR-373, miR-379, miR-494 and miR4487 that are likely to contribute to the disease pathophysiological process.

• The inhibitor set includes miR-7, miR-30, miR-34b/c, miR-124, miR-184, miR-205, miR-221* and miR-595 that are likely to inhibit the disease pathophysiological process.

• The third set consists of some miRNAs (e.g., let-7, miR-128 and miR-153) that can exert both beneficial and detrimental effects.

• There may be additional miRNAs involved in the pathogenesis of PD, which have hitherto remained unknown and thus further studies are needed to explore the issue.

Acknowledgement

The authors would like to thank the anonymous reviewers for their efforts and helpful suggestions.

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.