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Review
. 2023 Jun;51(6):50.
doi: 10.3892/ijmm.2023.5253. Epub 2023 May 5.

Autophagy‑regulating miRNAs: Novel therapeutic targets for Parkinson's disease (Review)

Zhenwang Ma #  1 , Hao Liang #  1 , Bingcheng Hu  1 , Shaojie Cai  2 , Dong Yan  3
Affiliations
Review

Autophagy‑regulating miRNAs: Novel therapeutic targets for Parkinson's disease (Review)

Zhenwang Ma et al. Int J Mol Med. 2023 Jun.

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder that has a high incidence during the aging process and is characterized by the loss of dopaminergic neurons in the substantia nigra, leading to motor dysfunctions and non‑motor symptoms. Impaired clearance and excessive accumulation of aberrantly modified proteins or damaged organelles, such as aggregated α‑synuclein and dysfunctional mitochondria, are regarded as the main causes of nigrostriatal neurodegeneration. As one of the major degradation pathways, autophagy can recycle these useless or toxic substances to maintain cellular homeostasis and it plays a crucial role in PD progression. MicroRNAs (miRNAs) are a group of small non‑coding RNA molecules that regulate gene expression by silencing targeted mRNAs. Recent studies have illustrated that autophagy‑regulating miRNA has been implicated in pathological processes of PD, including α‑synuclein accumulation, mitochondrial damage, neuroinflammation and neuronal apoptosis, which suggests that targeting autophagy‑regulating miRNAs may provide novel therapeutic strategies for this disease. The present review summarizes the role of autophagy in PD and emphasizes the role of miRNA‑mediated autophagy in PD, for the development of promising interventions in this disease.

Keywords: Parkinson's disease; autophagy; miRNAs; therapy; α‑synuclein.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
The regulatory role of miRNAs on the autophagy process in PD. Autophagy-related proteins and signaling pathways are regulated by miRNAs during each stage of autophagy, including initiation and nucleation, elongation, maturation, fusion and degradation. Both neuroprotective miRNAs (green) and neurotoxic miRNAs (red) are involved in the regulation of autophagy by targeting autophagy-related proteins and signaling pathways, thus affecting the pathogenesis of PD. → indicates a promoting effect and ┴ indicates an inhibitory effect. AMPK, adenosine monophosphate-activated protein kinase; ATG, autophagy-related gene; ERK, extracellular signal-regulated kinase; JNK, c-Jun N-terminal kinase; miR, microRNA; miRNA, microRNA; mTOR, mammalian target of rapamycin; PD, Parkinson's disease; PINK1, PTEN-induced putative kinase protein 1; PTEN, phosphatase and tensin homolog; ROS, reactive oxygen species; ULK1, unc-51-like kinase 1.
Figure 2
Figure 2
The roles of miRNA-mediated autophagy in PD progression. In the nucleus, a pri-mRNA is transcribed and further cleaved by Drosha and DGCR8 to generate pre-miRNA, which is cleaved into a miRNA duplex by Dicer and then is loaded to the groove of AGO to form the RISC complex. Both neuroprotective miRNAs (green) and neurotoxic miRNAs (red) are involved in the pathological processes of PD, including α-synuclein accumulation, mitochondrial damage, microglial activation and neuronal degeneration by modulating autophagy. AGO, Argonaute; PD, Parkinson's disease; pri-mRNA, primary microRNA; miR, microRNA; miRNA, microRNA; RISC, RNA-induced silencing complex.
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