Epigenetics Will Someday Transform the Science of Brain and Behavior

Mark F. Mehler, MD, discussed how brain and behavior are becoming better understood through the emerging discipline of epigenetics.

New Orleans, LA — During the Presidential Plenary Session of the 64th American Academy of Neurology annual meeting, Mark F. Mehler, MD, professor in the Departments of Neurology, Neurosciences and Psychiatry and Behavioral Sciences, and chairman of neurology at Albert Einstein College of Medicine in New York, discussed how brain and behavior are becoming better understood through the emerging discipline of epigenetics.

Epigenetics refers to the modification of gene expression and function not requiring primary changes in nucleotide sequence.

“Epigenetics will help us decipher several important questions in the clinical neurosciences,” said Dr Mehler. Dr Mehler also explained that through epigenetics new understanding will develop regarding the basis of gene-environmental interactions, the emergence and heritability of cognitive traits, the complexity of cellular identities and connectivity, the molecular pathogenesis of neuropsychiatric diseases, and the absence of neural regenerative potential.

“The Human Genome Project was supposed to usher in a new era of personalized medicine. Instead, it alerted us to the presence of a second, more sophisticated genome that needed to be studied,” said Dr Mehler.

Non-Coding RNA a Key Epigenetic Component

“Epigenetics is a combination of basic principles including DNA methylation, histone and chromatin remodeling, non-coding RNAs and RNA editing, an interrelated system in which all components work together to produce a powerful effect,” explained Dr Mehler.

Dr Mehler continued to discuss how epigenetics respond to metabolic and homeostatic environmental cues and regulate all areas of genome biology, including multigenerational heritability. His insight included the fact that epigenetics are essential for all cell functions and important for neurodevelopmental and adult brain function.

“We realize that the emerging genetic landscape encompasses not just protein coding genes but a very complex series of small and long non-coding RNAs. This complicated scheme brings us to an important insight that a single pathogenic mutation in a single base pair can not only affect the protein at the center, but the function of a universe of non-coding RNA networks as well. This helps explain the pathogenesis of complex neurological diseases,” Dr Mehler continued.

Epigenetic Applications Are Endless

According to Dr Mehler, the possibilities for harnessing epigenetics for therapeutic gain are “extraordinary.” These possibilities include the potential to recover lost learning and memory that seem irrevocably forfeited due to neurodegenerative disease. It is now known that these functions are potentially dormant and can be epigenetically reprogrammed through chromatin remodeling and exploitation of novel pathways.

Epigenetic reprogramming of cell identity, and of endogenous cells, is also possible, allowing cells or bioactive molecules to migrate to and remodel damaged or injured areas.

Epigenetic agents such as DNA methylation, histone and chromatin remodeling, non-coding RNA, and dynamic nuclear reprogramming that impact all aspects of the epigenome are either already available or in development. DNA demethylating agents and histone deacetylase inhibitors are clinically available. Histone methyltransferase inhibitors, histone demethylase inhibitors, histone kinase inhibitors, histone acetyltransferase inhibitors, bromodomain inhibitors, sirtuin inhibitors, and microRNA-related compounds are all in the pipeline.

“These are just the tip of the iceberg of what is possible,” Dr Mehler predicted.