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

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 a-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 a-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.