ArticleCellular and molecular life sciences : CMLS2024
Inhibition of EHMT1/2 rescues synaptic damage and motor impairment in a PD mouse model.
Article in Cellular and molecular life sciences : CMLS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 9 citations in OpenAlex.
- Epigenetic regulators polyphenols in neurodegenerative diseases: a promising intervention strategy.Annals of medicine · 2026Review
- Bioactivated Glucoraphanin Exerts a Potential Protective Effect in an In Vitro Model of Parkinson's Disease: A Transcriptomic Study.International journal of molecular sciences · 2026Article
- Lysine acetyltransferase 8-mediated histone acetylation, regulated by GBA1, is associated with lysosomal function related to α-Synuclein pathology.Cell death & disease · 2026Article
- Histone modification dynamics in brain aging: unlocking therapeutic potential.Cell death & disease · 2026Review
- Common pathogenic mechanisms in the hippocampus across neurodegenerative dementias: Alzheimer's disease, Down syndrome, and Parkinson's disease.NPJ dementia · 2026Article
- Epigenomic profile of GBA1 in Parkinson's disease.Parkinsonism & related disorders · 2025Article
- Article
- Epigenetic Modifiers: Exploring the Roles of Histone Methyltransferases and Demethylases in Cancer and Neurodegeneration.Biology · 2024Review
- Modifications on histone tails in Parkinson's disease.SciBase neurology · 2024Article
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Authors and funding
20 authors at 5 institutions in 1 country.
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Abstract
Epigenetic dysregulation that leads to alterations in gene expression and is suggested to be one of the key pathophysiological factors of Parkinson's disease (PD). Here, we found that α-synuclein preformed fibrils (PFFs) induced histone H3 dimethylation at lysine 9 (H3K9me2) and increased the euchromatic histone methyltransferases EHMT1 and EHMT2, which were accompanied by neuronal synaptic damage, including loss of synapses and diminished expression levels of synaptic-related proteins. Furthermore, the levels of H3K9me2 at promoters in genes that encode the synaptic-related proteins SNAP25, PSD95, Synapsin 1 and vGLUT1 were increased in primary neurons after PFF treatment, which suggests a linkage between H3K9 dimethylation and synaptic dysfunction. Inhibition of EHMT1/2 with the specific inhibitor A-366 or shRNA suppressed histone methylation and alleviated synaptic damage in primary neurons that were treated with PFFs. In addition, the synaptic damage and motor impairment in mice that were injected with PFFs were repressed by treatment with the EHMT1/2 inhibitor A-366. Thus, our findings reveal the role of histone H3 modification by EHMT1/2 in synaptic damage and motor impairment in a PFF animal model, suggesting the involvement of epigenetic dysregulation in PD pathogenesis.
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