Alzheimer's disease (AD)'s multifactorial nature stresses the role of epigenetics in affecting different pathological pathways. We demonstrated that one-carbon metabolism epigenetically impacts AD-lik Show more
Alzheimer's disease (AD)'s multifactorial nature stresses the role of epigenetics in affecting different pathological pathways. We demonstrated that one-carbon metabolism epigenetically impacts AD-like phenotype. Here, we investigated the crosstalk between methylation and microRNAs in AD. We altered one-carbon metabolism to induce hypo- and hyper-methylation, in SK-N-BE neuroblastoma cells and TgCRND8 mice. miRNAs were profiled through a polymerase chain reaction array, then we focused on miR-29a expression and methylation of its genomic locus. Finally, we assessed miR-29a expression and methylation in the brain of AD subjects. MiR-29a was repressed in hypomethylating and expressed in hypermethylating conditions. The expression of miR-29a and of its target, BACE1, was inversely correlated. We demonstrated for the first time that miR-29a is modulated by one-carbon metabolism through DNA methylation, disclosing the molecular mechanisms regulating BACE1 expression in AD. These data confirm miR-29a's protective role in AD and support miR-29a as a potential biomarker for AD. Show less
Besides its role in coagulation, vitamin K seems to be involved in various other mechanisms, including inflammation and age-related diseases, also at the level of gene expression. This work examined t Show more
Besides its role in coagulation, vitamin K seems to be involved in various other mechanisms, including inflammation and age-related diseases, also at the level of gene expression. This work examined the roles of two vitamin K2 (menaquinones) vitamers, namely, menaquinone-4 (MK4) and reduced menaquinone-7 (MK7R), as gene modulator compounds, as well as their potential role in the epigenetic regulation of genes involved in amyloidogenesis and neuroinflammation. The SK-N-BE human neuroblastoma cells provided a "first-line" model for screening the neuroinflammatory and neurodegenerative molecular pathways. MK7R, being a new vitamin K form, was first tested in terms of solubilization, uptake and cell viability, together with MK4 as an endogenous control. We assessed the expression of key factors in amyloidogenesis and neuroinflammation, observing that the MK7R treatment was associated with the downregulation of neurodegeneration- ( Show less