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

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.

Functional implications of NHR-210 enrichment in C. elegans cephalic sheath glia: insights into metabolic and mitochondrial disruptions in Parkinson's disease models

“…Our findings uncover a potential link between nhr-210 and pgp-9 dysregulation, mitochondrial dysfunction, and perturbations in dopamine synthesis, which aligns with the widely recognized role of mitochondrial damage and dopamine metabolism in the pathogenesis of Parkinson's disease [ 56 – 58 ]. Consequently, our work also suggests the possible therapeutic potential of targeting the nhr-210/pgp-9 pathway to maintain mitochondrial health, sustain metabolic homeostasis, and possibly slow the progression of neurodegenerative diseases.…”

“…The knockdown of pgp-9 not only disrupted mitochondrial homeostasis but also induced significant cellular apoptosis. This observation expands on the well-established concept of mitochondrial dysfunction leading to programmed cell death [ 51 – 55 ] and suggests that pgp-9 could be a pivotal player in the induction of mitochondrial-mediated apoptosis, a process implicated in neurodegeneration [ 56 – 58 ].…”

“…High-resolution magic angle spinning (HR-MAS) Nuclear Magnetic Resonance (NMR) based metabolomics, a robust tool for metabolic profiling, revealed alterations in key metabolic pathways, notably phenylalanine and tyrosine, precursors for dopamine synthesis. This links the dysregulation of mitochondrial functions to a potential disruption in dopamine synthesis, a neurotransmitter crucially implicated in several neurodegenerative diseases, particularly Parkinson's disease [ 56 – 58 ].…”

Autophagy‐associated non‐coding RNAs: Unraveling their impact on Parkinson's disease pathogenesis

“…miRNAs involved in autophagy regulation, such as miR‐155, miR‐181c, and miR‐214, contribute to PD pathogenesis by influencing α‐syn accumulation, mitochondrial damage, neuroinflammation, and neuronal apoptosis. Targeting these miRNAs holds promise for novel PD therapeutic strategies 198 . circRNAs are widely expressed in eukaryotes and have essential roles in NDs, including PD.…”

Alpha-Synuclein Contribution to Neuronal and Glial Damage in Parkinson’s Disease

“…Research advances continue to unveil a growing number of proteins and miRNA molecules as significant markers of autophagy dysfunction. It is crucial to increase our understanding of molecular factors implicated in PD pathogenesis, as it introduces a broader spectrum of potential targets for disease-modifying therapies [ 198 ].…”