microRNAs in Parkinson's Disease: From Pathogenesis to Novel Diagnostic and Therapeutic Approaches

Int J Mol Sci. 2017 Dec 13;18(12):2698. doi: 10.3390/ijms18122698.

Abstract

Parkinson's disease (PD) is the most prevalent central nervous system (CNS) movement disorder and the second most common neurodegenerative disease overall. PD is characterized by the progressive loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc) within the midbrain, accumulation of alpha-synuclein (α-SYN) in Lewy bodies and neurites and excessive neuroinflammation. The neurodegenerative processes typically begin decades before the appearance of clinical symptoms. Therefore, the diagnosis is achievable only when the majority of the relevant DAergic neurons have already died and for that reason available treatments are only palliative at best. The causes and mechanism(s) of this devastating disease are ill-defined but complex interactions between genetic susceptibility and environmental factors are considered major contributors to the etiology of PD. In addition to the role of classical gene mutations in PD, the importance of regulatory elements modulating gene expression has been increasingly recognized. One example is the critical role played by microRNAs (miRNAs) in the development and homeostasis of distinct populations of neurons within the CNS and, in particular, in the context of PD. Recent reports demonstrate how distinct miRNAs are involved in the regulation of PD genes, whereas profiling approaches are unveiling variations in the abundance of certain miRNAs possibly relevant either to the onset or to the progression of the disease. In this review, we provide an overview of the miRNAs recently found to be implicated in PD etiology, with particular focus on their potential relevance as PD biomarkers, as well as their possible use in PD targeted therapy.

Keywords: biomarkers; exosomes; microRNAs; neuroprotective therapies; parkinson’s disease.

Publication types

  • Review

MeSH terms

  • Antagomirs / therapeutic use
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Biomarkers / metabolism
  • Exosomes / metabolism
  • Humans
  • MicroRNAs / analysis
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Neuroprotective Agents / therapeutic use
  • Parkinson Disease / diagnosis*
  • Parkinson Disease / pathology
  • Parkinson Disease / therapy
  • Protein Deglycase DJ-1 / antagonists & inhibitors
  • Protein Deglycase DJ-1 / genetics
  • Protein Deglycase DJ-1 / metabolism
  • Ubiquitin-Protein Ligases / antagonists & inhibitors
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • alpha-Synuclein / antagonists & inhibitors
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism

Substances

  • Antagomirs
  • Biomarkers
  • MicroRNAs
  • Neuroprotective Agents
  • SNCA protein, human
  • alpha-Synuclein
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Protein Deglycase DJ-1