CpG and non-CpG methylation in the diet-epigenetics-neurodegeneration connection

PURPOSE OF REVIEW: Unraveling the diet-epigenetics-neurodegeneration connection may disclose associated mechanisms and novel approaches to the neurodegenerative diseases. This review summarizes the basic concepts and the innovative results in this field focusing on the relevance of non-CpG methylation. RECENT FINDINGS: Many multifactorial neurodegenerative diseases are associated with epigenetic changes, and the brain seems more prone to epigenetic changes than other tissues. Several environmental factors induce epigenetic modulation in the organisms: diet and nutrition retain a high capacity to modulate the epigenetic traits. Finally, unexpected, specific, and functional non-CpG methylation in the brain was identified. Non-CpG methylation modulates brain expression of genes especially in promoters characterized by low-density CpGs distribution. These genes appear more prone to the epigenetic effect of environmental factors, i.e., diet, possibly inducing neurodegenerative processes. Understanding these processes could help in setting nutritional intervention aimed at contrasting neurodegenerative diseases.