miR-124 and Parkinson's disease: A biomarker with therapeutic potential

Pharmacol Res. 2019 Dec;150:104515. doi: 10.1016/j.phrs.2019.104515. Epub 2019 Nov 7.

Abstract

Parkinson's disease (PD) is a multifactorial disorder, attributed to a complex interplay between genetic and epigenetic factors. Although the exact etiology of the disease remains elusive, dysregulation of signaling pathways implicated in cell survival, apoptosis, protein aggregation, mitochondrial dysfunction, autophagy, oxidative damage and neuroinflammation, contributes to its pathogenesis. MicroRNAs (miRs) are endogenous short non-coding RNA molecules that negatively regulate gene expression at a post-transcriptional level. MiR-124 is one of the most abundantly expressed miRs in the brain that participates in neurogenesis, synapse morphology, neurotransmission, inflammation, autophagy and mitochondrial function. Accumulating pre-clinical evidence shows that miR-124 may act through calpain 1/p25/cyclin-dependent kinases 5 (CDK5), nuclear factor-kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), Bcl-2-interacting mediator of cell death (Bim), 5' adenosine monophosphate-activated protein kinase (AMPK) and extracellular signal-regulated kinase (ERK)-mediated pathways to regulate cell survival, apoptosis, autophagy, mitochondrial dysfunction, oxidative damage and neuroinflammation in PD. Moreover, clinical evidence indicates that reduced plasma miR-124 levels may serve as a potential diagnostic biomarker in PD. This review provides an update of the pathogenic implication of miR-124 activity in PD and discusses its targeting potential for the development of future therapeutic strategies.

Keywords: Biomarker; Neuroinflammation; Neuroprotection; Parkinson’s disease; miR-124.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers / blood
  • Humans
  • MicroRNAs* / blood
  • Neuroprotection
  • Parkinson Disease / blood
  • Parkinson Disease / drug therapy
  • Parkinson Disease / genetics*

Substances

  • Biomarkers
  • MIRN124 microRNA, human
  • MicroRNAs