Genetic and Epigenetic Mechanisms of Parkinson's Disease

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Background

The understanding of the genetic basis of Parkinson’s disease (PD) has greatly developed over the past decades, since the discovery of SNCA gene mutation, which results in familial autosomal dominant PD. To date, at least 23 loci and 19 disease-causing genes for Parkinsonism, as well as genetic risk loci and sporadic PD phenotype genetic variants, have been identified in various association studies. However, the exact biological functions and pathogenic contributions of these genes to this complex disorder are still far from being clearly understood. Additional genes are expected to be extensively investigated in the near future, thanks to the application of genome-wide technology to better understand the pathogenesis of both familial and sporadic PD.

Growing evidence has suggested that epigenetic mechanisms might also contribute to the disease pathogenesis, in addition to genetic mutations. For instance, studies have revealed an upregulated SNCA gene expression resulting from promoter demethylation in PD patients’ brains. α-Synuclein itself exerts epigenetic properties, such as histone tail modifications and DNMT1 sequestration. In addition, microRNAs are also able to modulate α-synuclein expression levels. Other PD-related genes have been found to be regulated by promoter methylation or RNA-mediated mechanisms. For example, a decrease in the expression of DJ1 and parkin proteins can result from microRNA-mediated mechanisms in PD brains. Increasing studies aiming to explore the epigenetic basis of PD have helped to better understand the molecular mechanisms involved in dopaminergic neuron loss, as well as providing grounds to examine the potential of epigenetic modifying strategy to counteract PD.

Future research in PD should aim to understand and further dissect the complex interplay between the genetic basis and epigenetic biomarkers, lifestyles, and environmental factors, to characterize individuals at risk, and develop novel therapeutic approaches.

This Research Topic aims to collect research contributions, unraveling the mechanism by which epigenetic modifications (i.e., DNA methylation, histone modifications and ncRNAs) interact with genes and environmental factors leading to PD pathogenesis. We welcome original research and review articles covering, but not limited to, the following themes:

1. Integrative genomics studies identify new genes associated with PD;
2. Epigenetic and microRNA-related studies identify PD pathogenesis mechanisms and potential therapeutic targets for PD
3. Gene-Environment studies Identify PD modifier gene or risk gene via Interaction with various environmental factors
4. Genetic studies and statistical analysis identify the interactions between SNPs associated with PD risk and potential biological mechanisms
5. Disease mechanisms studies using omics approaches and new animal models

Keywords: Genetic, Epigenetic, Parkinson's Disease, MicroRNA

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