Lysine methylation: Implications in neurodegenerative disease

Lysine methylation is well-documented and relatively well-understood with respect to histone modification and the epigenetic regulation of gene expression. Enzymes called lysine methyltransferases (KMTs) are capable of methylating lysine residues on histone tails, while the opposing lysine demethylases (KDMs) are capable of removing the methyl groups. This balance of dynamic methylation of histone proteins effectively alters gene expression, and has been widely studied with many applications in neurological disease. While histone methylation is an extensive field of research, lysine methylation has received considerable attention in recent years, following the discovery of a handful of non-histone substrates for KMTs. With the expanding repertoire of nonhistone substrates, exploration into the cellular functions regulated by this dynamic post-translational modification has become an intriguing research question. Recent studies have implicated non-histone methylation in many crucial cell processes, such as signal transduction, apoptosis, and proliferation. Although most of the current research in this emerging field is streamlined for applications in cancer, it seems that lysine methylation of non-histone proteins could also be relevant in neurodegenerative disease. This review will summarize what is known about the role of histone lysine methylation in neurodegenerative diseases, and explore the links between recently identified non-histone methylated proteins, and the brain. Our goal is to connect the emerging field of non-histone protein methylation with neurodegenerative research.