Epigenetic Changes in Prion and Prion-like Neurodegenerative Diseases: Recent Advances, Potential as Biomarkers, and Future Perspectives

Abstract

Prion diseases are transmissible spongiform encephalopathies (TSEs) caused by a conformational conversion of the native cellular prion protein (PrP^C) to an abnormal, infectious isoform called PrP^Sc. Amyotrophic lateral sclerosis, Alzheimer's, Parkinson's, and Huntington's diseases are also known as prion-like diseases because they share common features with prion diseases, including protein misfolding and aggregation, as well as the spread of these misfolded proteins into different brain regions. Increasing evidence proposes the involvement of epigenetic mechanisms, namely DNA methylation, post-translational modifications of histones, and microRNA-mediated post-transcriptional gene regulation in the pathogenesis of prion-like diseases. Little is known about the role of epigenetic modifications in prion diseases, but recent findings also point to a potential regulatory role of epigenetic mechanisms in the pathology of these diseases. This review highlights recent findings on epigenetic modifications in TSEs and prion-like diseases and discusses the potential role of such mechanisms in disease pathology and their use as potential biomarkers.

Keywords: DNA methylation; epigenetics; histone modifications; microRNA; prion diseases; prion-like diseases.

Figure 1

Comparison of differentially methylated regions (DMRs) and positions (DMPs) in prion-like diseases. Venn diagrams indicate the number of common and unique DMRs (a) and DMPs (b) in AD, PD, ALS, and HD.

Figure 2

Venn diagrams of miRNA profiles in prion-like diseases: (a) upregulated miRNAs in prion-like disease patients; (b) downregulated miRNAs in patients suffering from prion-like diseases.