Epigenetic regulation in Parkinson’s disease

Catherine Labbé, Oswaldo Lorenzo-Betancor, Owen A. Ross

Research output: Contribution to journalReview articlepeer-review

34 Scopus citations

Abstract

Recent efforts have shed new light on the epigenetic mechanisms driving gene expression alterations associated with Parkinson’s disease (PD) pathogenesis. Changes in gene expression are a well-established cause of PD, and epigenetic mechanisms likely play a pivotal role in regulation. Studies in families with PD harboring duplications and triplications of the SNCA gene have demonstrated that gene dosage is associated with increased expression of both SNCA mRNA and protein, and correlates with a fulminant disease course. Furthermore, it is postulated that even subtle changes in SNCA expression caused by common variation is associated with disease risk. Of note, genome-wide association studies have identified over 30 loci associated with PD with most signals located in non-coding regions of the genome, thus likely influencing transcript expression levels. In health, epigenetic mechanisms tightly regulate gene expression, turning genes on and off to balance homeostasis and this, in part, explains why two cells with the same DNA sequence will have different RNA expression profiles. Understanding this phenomenon will be crucial to our interpretation of the selective vulnerability observed in neurodegeneration and specifically dopaminergic neurons in the PD brain. In this review, we discuss epigenetic mechanisms, such as DNA methylation and histone modifications, involved in regulating the expression of genes relevant to PD, RNA-based mechanisms, as well as the effect of toxins and potential epigenetic-based treatments for PD.

Original languageEnglish (US)
Pages (from-to)515-530
Number of pages16
JournalActa neuropathologica
Volume132
Issue number4
DOIs
StatePublished - Oct 1 2016

Keywords

  • Acetylation
  • Epigenetics
  • Histones
  • Methylation
  • Parkinson’s disease
  • RNA-based epigenetic mechanisms

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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