ArticleHuman molecular genetics2022
Altered hydroxymethylome in the substantia nigra of Parkinson's disease.
Article in Human molecular genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Genome-Wide Meta-Analysis of Parkinson's Disease Associated Genetic Loci and Validation of Therapeutic Targets.Brain and behavior · 2025Pooled it
- Comparative validation of oxidative bisulfite sequencing (oxBS) and chemical-assisted pyridine borane sequencing (CAPS) protocols for locus-specific 5-hydroxymethylcytosine quantification.Epigenetics & chromatin · 2026Article
- Profiling of 5-hydroxymethylcytosine in blood reveals preferential enrichment at exon-intron junctions and predictive value for Parkinson's disease.NPJ Parkinson's disease · 2026Article
- Epigenetic mechanisms of Parkinson's disease and potential epigenetic-based therapeutics.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Emerging Potential of Ras-proximate-1 (Rap1) in Mediating Neurodegenerative Diseases.Current neuropharmacology · 2026Review
- Parkinson's disease-associated alterations in DNA methylation and hydroxymethylation in human brain.NPJ Parkinson's disease · 2025Article
- 5-Hydroxymethylcytosine: Far Beyond the Intermediate of DNA Demethylation.International journal of molecular sciences · 2024Review
- Methods for Detection and Mapping of Methylated and Hydroxymethylated Cytosine in DNA.Biomolecules · 2024Review
- Tet1-mediated activation of the Ampk signaling by Trpv1 DNA hydroxymethylation exerts neuroprotective effects in a rat model of Parkinson's disease.Functional & integrative genomics · 2024Article
- Parkinson's disease-associated shifts between DNA methylation and DNA hydroxymethylation in human brain in PD-related genes, including PARK19 (DNAJC6) and PTPRN2 (IA-2β).Research square · 2024Article
- An Overview of Epigenetic Changes in the Parkinson's Disease Brain.International journal of molecular sciences · 2024Review
- Unraveling the Epigenetic Landscape: Insights into Parkinson's Disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis.Brain sciences · 2024Review
- Phospholipase D, a Novel Therapeutic Target Contributes to the Pathogenesis of Neurodegenerative and Neuroimmune Diseases.Analytical cellular pathology (Amsterdam) · 2024Review
- Review
- Epigenetic modification in Parkinson's disease.Frontiers in cell and developmental biology · 2023Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Parkinson's disease (PD) is the second most common neurodegenerative disorder, and aging and genetic and environmental exposure can contribute to its pathogenesis. DNA methylation has been suggested to play a pivotal role in neurodevelopment and neurodegenerative diseases. 5-hydroxymethylcytosine (5hmC) is generated through 5-methylcytosine (5mC) oxidization by ten-eleven translocation proteins and is particularly enriched in the brain. Although 5hmC has been linked to multiple neurological disorders, little is known about 5hmC alterations in the substantia nigra of patients with PD. To determine the specific alterations in DNA methylation and hydroxymethylation in PD brain samples, we examined the genome-wide profiles of 5mC and 5hmC in the substantia nigra of patients with PD and Alzheimer's disease (ad). We identified 4119 differentially hydroxymethylated regions (DhMRs) and no differentially methylated regions (DMRs) in the postmortem brains of patients with PD compared with those of controls. These DhMRs were PD-specific when compared with the results of AD. Gene ontology analysis revealed that several signaling pathways, such as neurogenesis and neuronal differentiation, were significantly enriched in PD DhMRs. KEGG enrichment analysis revealed substantial alterations in multiple signaling pathways, including phospholipase D (PLD), cAMP and Rap1. In addition, using a PD Drosophila model, we found that one of the 5hmC-modulated genes, PLD1, modulated α-synuclein toxicity. Our analysis suggested that 5hmC may act as an independent epigenetic marker and contribute to the pathogenesis of PD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.