From epigenetic scripts to kinase signals: linking DOT1L and RIPK1 in the neurobiology of degeneration.

With growing insights into brain networks and neurodegenerative diseases (NDDs), it has become evident that alterations in gene expression often arise from epigenetic regulation rather than changes in DNA sequence. Consequently, extensive research has centered on understanding the epigenetic role in the pathophysiology of Alzheimer's, Parkinson's, and Huntington's disease. Epigenetic modifications are essential for maintaining cellular homeostasis by dynamically controlling gene expression, and their characterization may provide greater understanding into disease mechanisms and potential therapeutic targets. A deeper understanding of these regulatory processes may offer valuable insights into disease mechanisms and reveal new therapeutic avenues. Despite significant progress, the influence of epigenetic modifiers on intracellular signaling pathways governing neuronal survival and degeneration remains poorly understood. Notably, the interaction between DOT1L-mediated histone methylation and RIPK1 signalling is still insufficiently explored, representing an important gap in current knowledge. This review emphasizes the emerging interplay between DOT1L and RIPK1 in the regulation of the cell-death pathway, underscoring their potential role in modulating neuronal survival in NDDs.