Epigenomics of neurological disorders

Neurological disorders, including Alzheimer’s and Parkinson’s diseases, Dravet syndrome, amyotrophic lateral sclerosis, Angelman syndrome, fragile X mental retardation, spinal muscular atrophy, and many others, affect a significant part of world population. The proportion of familial cases in many of these disorders is small, indicating a significant role of environment, de novo mutations, multigenic predispositions, and epigenetic changes in their pathogenesis. Epigenetic changes in particular have been the subject of intense investigation in recent years. Besides epigenetic DNA and histone modification enzymes, long noncoding RNAs (lncRNAs) are emerging as essential components of epigenetic regulation. lncRNAs represent a major interest in the drug development process because they provide access to previously “undruggable” gene targets. Furthermore, lncRNA can be modulated using oligonucleotide-based compounds that have a shortened development pipeline. The synergy of the novel disease mechanisms (epigenetics), new therapeutic target class (lncRNA), an optimal therapeutic modality (oligonucleotide-based compounds), and unmet medical need in sporadic cases of major neurological disorders fuels intensive research in this area. We briefly review these studies.