Ricerc@Sapienza

Recent evidence emphasizes the role of dysregulated one-carbon metabolism in Alzheimer's Disease (AD). Exploiting a nutritional B-vitamin deficiency paradigm, we have previously shown that PSEN1 and BACE1 activity is modulated by one-carbon metabolism, leading to increased amyloid production. We have also demonstrated that S-adenosylmethionine (SAM) supplementation contrasted the AD-like features, induced by B-vitamin deficiency. In the present study, we expanded these observations by investigating the effects of SAM and SOD (Superoxide dismutase) association.

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.

The short, non-coding RNAs, also called microRNAs (miRNAs) can bind complementary sequences on cellular mRNAs. The consequence of this binding is generally the degradation of mRNA and the inhibition of its translation. For this reason, miRNAs are included among the epigenetic factors acting as a modulator of gene expression. How miRNAs expression is, in turn, regulated is still the object of active investigation, but DNA methylation, another epigenetic modification, seems to play a central role in this sense.