Modifications on histone tails in Parkinson's disease.

This study investigates the role of histone tail modifications in Parkinson's disease (PD), emphasizing the epigenetic regulation of genes associated with the disease. PD primarily manifests in individuals over 60, suggesting that PD-causal genes remain dormant until later in life, influenced by environmental factors and epigenetic modifications. Histone modifications such as methylation, acetylation, phosphorylation, and ubiquitylation play crucial roles in gene expression regulation by altering chromatin structure or interacting with gene regulatory regions. Specifically, modifications on histones H2A, H2AX, H3, and H4 have been linked to PD. For instance, α-synuclein (α-SYN) aggregation, a hallmark of PD, is regulated by histone modifications like H3K27ac and H3K4me3, which enhance α-SYN expression and contribute to PD progression. Conversely, repressive marks like H3K9ac and H3K27me3 can mitigate PD risk by reducing α-SYN levels. Therapeutic strategies targeting these histone modifications, such as the use of GSK-J4 or vitamin C-treated neural stem cells, show potential in alleviating PD symptoms by modulating histone marks and gene expression. Understanding these epigenetic mechanisms offers promising avenues for developing novel treatments for PD.