ArticleHuman molecular genetics2022
Alpha-synuclein overexpression induces epigenomic dysregulation of glutamate signaling and locomotor pathways.
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 10 papers.
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Who cites it
10 citing papers in PubMed, 10 citations in OpenAlex.
- Neurobiology of exercise in Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Retinoic acid alleviates manganese-induced neurotoxicity in SH-SY5Y cells via the Trim28/α-synuclein/H4K91ac epigenetic axis.Frontiers in pharmacology · 2026Article
- Review
- Umbilical cord blood-derived exosomes attenuate dopaminergic neuron damage of Parkinson's disease mouse model.Journal of nanobiotechnology · 2024Article
- Brain Region-Specific Expression Levels of Synuclein Genes in an Acid Sphingomyelinase Knockout Mouse Model: Correlation with Depression-/Anxiety-Like Behavior and Locomotor Activity in the Absence of Genotypic Variation.International journal of molecular sciences · 2024Article
- Unraveling the Complex Interplay between Alpha-Synuclein and Epigenetic Modification.International journal of molecular sciences · 2023Review
- α-Synuclein and Mechanisms of Epigenetic Regulation.Brain sciences · 2023Review
- Cellular Models of Alpha-Synuclein Aggregation: What Have We Learned and Implications for Future Study.Biomedicines · 2022Review
- CK2 alpha prime and alpha-synuclein pathogenic functional interaction mediates synaptic dysregulation in huntington's disease.Acta neuropathologica communications · 2022Article
- DNA methylation as a mediator of genetic and environmental influences on Parkinson's disease susceptibility: Impacts of alpha-Synuclein, physical activity, and pesticide exposure on the epigenome.Frontiers in genetics · 2022Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Parkinson's disease (PD) is a neurological disorder with complex interindividual etiology that is becoming increasingly prevalent worldwide. Elevated alpha-synuclein levels can increase risk of PD and may influence epigenetic regulation of PD pathways. Here, we report genome-wide DNA methylation and hydroxymethylation alterations associated with overexpression of two PD-linked alpha-synuclein variants (wild-type and A30P) in LUHMES cells differentiated to dopaminergic neurons. Alpha-synuclein altered DNA methylation at thousands of CpGs and DNA hydroxymethylation at hundreds of CpGs in both genotypes, primarily in locomotor behavior and glutamate signaling pathway genes. In some cases, epigenetic changes were associated with transcription. SMITE network analysis incorporating H3K4me1 ChIP-seq to score DNA methylation and hydroxymethylation changes across promoters, enhancers, and gene bodies confirmed epigenetic and transcriptional deregulation of glutamate signaling modules in both genotypes. Our results identify distinct and shared impacts of alpha-synuclein variants on the epigenome, and associate alpha-synuclein with the epigenetic etiology 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.