DNA methylation in neurodegenerative disorders: a missing link between genome and environment?

The risk of developing neurodegenerative disorders such as Alzheimer's disease or Parkinson's disease is influenced by genetic and environmental factors. Environmental events occurring during development or later in life can be related to disease susceptibility. One way by which the environment may exert its effect is through epigenetic modifications, which might affect the functioning of genes. These include nucleosome positioning, post-translational histone modifications, and DNA methylation. In this review we will focus in the potential role of DNA methylation in neurodegenerative disorders and in the approaches to explore such epigenetic changes. Advances in deciphering the role of epigenetic modifications in phenotype are being uncovered for a variety of diseases, including cancer, autoimmune, neurodevelopmental and cognitive disorders. Epigenetic modifications are now being also associated with cardiovascular and metabolic traits, and they are expected to be especially involved in learning and memory processes, as well as in neurodegenerative disease. The study of the role of methylation and other epigenetic modifications in disease development will provide new insights in the etiopathogenesis of neurodegenerative disorders, and should hopefully shape new avenues in the development of therapeutic strategies.