Neurodegenerative movement disorders (NMDs) are age-dependent disorders that are characterised by the degeneration and loss of neurons, typically accompanied by pathological accumulation of different protein aggregates in the brain, which lead to motor symptoms. NMDs include Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, and Huntington's disease, among others. Epigenetic modifications are responsible for functional gene regulation during development, adult life and ageing and have progressively been implicated in complex diseases such as cancer and more recently in neurodegenerative diseases, such as NMDs. DNA methylation is by far the most widely studied epigenetic modification and consists of the reversible addition of a methyl group to the DNA without changing the DNA sequence. Although this research field is still in its infancy in relation to NMDs, an increasing number of studies point towards a role for DNA methylation in disease processes. This review addresses recent advances in epigenetic and epigenomic research in NMDs, with a focus on human brain DNA methylation studies. We discuss the current understanding of the DNA methylation changes underlying these disorders, the potential for use of these DNA modifications in peripheral tissues as biomarkers in early disease detection, classification and progression as well as a promising role in future disease management and therapy.
IntroductionPatients with Parkinson disease (PD) tend to have ophthalmic symptoms. Retinal diseases are associated with central nervous system diseases, especially neurodegenerative diseases. Here, we investigated the association of retinal diseases with PD, especially the temporal relationship before and after PD diagnosis.MethodsData were obtained from the National Health Insurance Research Database of Taiwan. In total, 21,845 patients with newly diagnosed PD were matched with four controls each on the basis of propensity score. This study was bidirectional. A case–control study evaluated the adjusted odds ratio (aOR) of retinal disease before PD diagnosis by using conditional logistic regression. Furthermore, a cohort study evaluated the adjusted subdistribution hazard ratio (aSHR) for new-onset retinal and optic nerve diseases after PD diagnosis by using competing risk analysis. The association between PD with optic nerve diseases and glaucoma (another common ophthalmic diseases with the consequence of retinal dysfunction) were also analyzed as reference.ResultsIn the case–control study, PD was found to be significantly comorbid with recent and remote retinal disease [recent: ≤ 5 years, aOR: 1.12, 95% confidence interval (CI): 1.03–1.23; remote: > 5 years, aOR: 1.18, 95% CI: 1.04–1.34]. No similar association was identified between optic nerve disease or glaucoma with PD. In the cohort study, patients with PD were found to have a low risk of retinal disease in short-term (≤ 5 years, aSHR: 0.81, 95% CI: 0.71–0.93) and long-term (> 5 years, aSHR: 0.82, 95% CI: 0.72–0.93) follow-up.ConclusionThe study findings demonstrated that patients with prediagnostic PD were at greater risk of retinal disease than non-PD participants, but the risk reversed afterward. Thus, retinal disease may be a premotor manifestation of PD, and there may be some possible effect of dopamine supplements on retina.
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