Developing epigenetic diagnostics and therapeutics for brain disorders

• Epigenetic signatures found in central and peripheral nervous system disease patient-derived tissues correlate with pathological features and clinical outcomes.
• Emerging technological advances are allowing integrated epigenomic profiling.
• Compounds for modulating targets across the entire spectrum of epigenetic writer, eraser, and reader classes and non-coding RNA pathways are being developed.

Perturbations in epigenetic mechanisms have emerged as cardinal features in the molecular pathology of major classes of brain disorders. We therefore highlight evidence which suggests that specific epigenetic signatures measurable in central – and possibly even in peripheral tissues – have significant value as translatable biomarkers for screening, early diagnosis, and prognostication; developing molecularly targeted medicines; and monitoring disease progression and treatment responses. We also draw attention to existing and novel therapeutic approaches directed at epigenetic factors and mechanisms, including strategies for modulating enzymes that write and erase DNA methylation and histone/chromatin marks; protein–protein interactions responsible for reading epigenetic marks; and non-coding RNA pathways.