R-loop Homeostasis and Chromatin-Associated Transcription Stress in Neuronal Aging and Neurodegeneration

R-loop biology sits at the intersection of transcription, chromatin regulation, and genome maintenance. Although R-loops can support normal gene regulation, their persistence or dysregulation may disrupt transcription and promote DNA damage. These challenges are especially important in post-mitotic neurons, which must preserve genomic and transcriptional integrity throughout life. Research is connecting unresolved R-loops and related transcriptional stress with altered chromatin organization, impaired RNA processing, DNA damage responses, and neurodegenerative processes. However, how these mechanisms interact over time, contribute to neuronal dysfunction, and vary across disease contexts remains incompletely understood. Further investigation is needed to clarify the causal relationships and identify which findings generalize across models and human disease.This Research Topic aims to advance understanding of how R-loop homeostasis and chromatin-associated transcriptional stress affect genome maintenance, chromatin architecture, epigenetic regulation, gene-expression programs, and neuronal function during aging and neurodegeneration. We welcome studies examining the mechanisms that govern R-loop formation and resolution, their consequences for neuronal health, and the circumstances in which downstream pathways; including cGAS–STING signaling; are engaged.To gather further insights into R-loop-related mechanisms in neuronal biology, aging, and neurodegenerative disease, we welcome work in cellular, animal, and human-derived systems. Comparative studies of cancer, developmental disease, or cellular senescence are also in scope when they clarify mechanisms relevant to these areas. Themes include, but are not limited to:- Mechanisms controlling R-loop formation, processing, and resolution- R-loops, DNA damage responses, and genome instability in neurons- Effects of transcriptional stress on RNA processing, export, and gene expression- R-loop-associated changes in chromatin organization and epigenetic regulation- Links between unresolved R-loops, cGAS–STING signaling, and neuronal function- R-loops in ALS/FTD, Alzheimer’s disease, ataxias, and repeat-expansion disorders- Comparative and mechanistic studies using yeast, Drosophila, organoids, and iPSC-derived models- Connections between neuronal aging, cellular senescence, and neurodegenerationContributions may include original research, reviews, and methodological studies. Topic editors: Hana Hall, Priyanka Soni Source: https://www.frontiersin.org/research-topics/86714/r-loop-homeostasis-and-chromatin-associated-transcription-stress-in-neuronal-aging-and-neurodegeneration