miR-221 and Parkinson's disease: A biomarker with therapeutic potential

Eur J Neurosci. 2024 Jan;59(2):283-297. doi: 10.1111/ejn.16207. Epub 2023 Dec 3.

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, leading to various motor and non-motor symptoms. Several cellular and molecular mechanisms such as alpha-synuclein (α-syn) accumulation, mitochondrial dysfunction, oxidative stress and neuroinflammation are involved in the pathogenesis of this disease. MicroRNAs (miRNAs) play important roles in post-transcriptional gene regulation. They are typically about 21-25 nucleotides in length and are involved in the regulation of gene expression by binding to the messenger RNA (mRNA) molecules. miRNAs like miR-221 play important roles in various biological processes, including development, cell proliferation, differentiation and apoptosis. miR-221 promotes neuronal survival against oxidative stress and neurite outgrowth and neuronal differentiation. Additionally, the role of miR-221 in PD has been investigated in several studies. According to the results of these studies, (1) miR-221 protects PC12 cells against oxidative stress induced by 6-hydroxydopamine; (2) miR-221 prevents Bax/caspase-3 signalling activation by stopping Bim; (3) miR-221 has moderate predictive power for PD; (4) miR-221 directly targets PTEN, and PTEN over-expression eliminates the protective action of miR-221 on p-AKT expression in PC12 cells; and (5) miRNA-221 controls cell viability and apoptosis by manipulating the Akt signalling pathway in PD. This review study suggested that miR-221 has the potential to be used as a clinical biomarker for PD diagnosis and stage assignment.

Keywords: Parkinson's disease; biomarkers; miR-221; neuroprotection.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers / metabolism
  • Dopaminergic Neurons / metabolism
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Parkinson Disease* / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats

Substances

  • Proto-Oncogene Proteins c-akt
  • MicroRNAs
  • Biomarkers
  • MIRN221 microRNA, human
  • MIRN221 microRNA, rat