DNA Methylation changes in the brain white matter of multiple sclerosis patients

The literature implies that Multiple Sclerosis (MS) holds an epigenetic component that mediates the effects of its typical environmental risk factors on disease progression. Some of the major epigenetic modifications on DNA are the addition of methyl or a hydroxymethyl group to the C5 cytosine position, leading to 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) synthesis. Interestingly, abnormal epigenetic modification patterns, such as the global DNA methylation loss in MS brain white matter, link to several neurodegenerative disorders. Abnormal DNA methylation/hydroxymethylation enzymes expression is also extensively documented in Alzheimer’s disease and cancer. This doctoral research project traces the DNA methylation instability in MS white matter, back to the altered expression of the DNA methylation/hydroxymethylation enzymes

DNA methylation dynamics in aging: How far are we from understanding the mechanisms?

DNA methylation is currently the most promising molecular marker for monitoring aging and predicting life expectancy. However, the mechanisms underlying age-related DNA methylation changes remain mostly undiscovered.Here we discuss the current knowledge of the dynamic nature of DNA epigenome landscape in mammals, and propose putative molecular mechanisms for aging-associated DNA epigenetic changes. Specifically, we describe age-related variations of methylcytosine and its oxidative derivatives in relation to the dynamics of chromatin structure, histone post-translational modifications and their modulators.Finally, we are proposing a conceptual framework that could explain the complex nature of the effects of age on DNA methylation patterns. This combines the accumulation of DNA methylation noise and also all of the predictable, site-specific DNA methylation changes.Gathering information in this area would pave the way for future investigation aimed at establishing a possible causative role of epigenetic mechanisms in aging

Counteracting aged DNA methylation states to combat ageing and age-related diseases

DNA methylation (DNAm) overwrites information about multiple extrinsic factors on the genome. Age is one of these factors. Age causes characteristic DNAm changes that are thought to be not only major drivers of normal ageing but also precursors to diseases, cancer being one of these. Although there is still much to learn about the relationship between ageing, age-related diseases and DNAm, we now know how to interpret some of the effects caused by age in the form of changes in methylation marks at specific loci. In fact, these changes form the basis of the so called "epigenetic clocks", which translate the genomic methylation profile into an "epigenetic age". Epigenetic age does not only estimate chronological age but can also predict the risk of chronic diseases and mortality. Epigenetic age is believed to be one of the most accurate metrics of biological age. Initial evidence has recently been gathered pointing to the possibility that the rate of epigenetic ageing can be slowed down or even reversed. In this review, we discuss some of the most relevant advances in this field. Expected outcome is that this approach can provide insights into how to preserve health and reduce the impact of ageing diseases in humans

Increased PARylation impacts the DNA methylation process in type 2 diabetes mellitus

Epigenetic modifications, such as DNA methylation, can influence the genetic susceptibility to type 2 diabetes mellitus (T2DM) and the progression of the disease. Our previous studies demonstrated that the regulation of the DNA methylation pattern involves the poly(ADP-ribosyl)ation (PARylation) process, a post-translational modification of proteins catalysed by the poly(ADP-ribose) polymerase (PARP) enzymes. Experimental data showed that the hyperactivation of PARylation is associated with impaired glucose metabolism and the development of T2DM. Aims of this case-control study were to investigate the association between PARylation and global and site-specific DNA methylation in T2DM and to evaluate metabolic correlates

Novel optimized biopolymer-based nanoparticles for nose-to-brain delivery in the treatment of depressive diseases

A valid option to bypass the obstacle represented by the blood–brain barrier (BBB) in brain delivery is the use of the unconventional intranasal route of administration

Sensitivity to heavy-metal ions of unfolded fullerene quantum dots

A novel type of graphene-like quantum dots, synthesized by oxidation and cage-opening of C60buckminsterfullerene, has been studied as a ï¬\u82uorescent and absorptive probe for heavy-metal ions. The lattice structure of such unfolded fullerene quantum dots (UFQDs) is distinct from that of graphene since it includes both carbon hexagons and pentagons. The basic optical properties, however, are similar to those of regular graphene oxide quantum dots. On the other hand, UFQDs behave quite differently in the presence of heavy-metal ions, in that multiple sensitivity to Cu2+, Pb2+and As(III) was observed through comparable quenching of the ï¬\u82uorescent emission and different variations of the transmittance spectrum. By dynamic light scattering measurements and transmission electron microscope (TEM) images we conï¬\u81rmed, for the ï¬\u81rst time in metal sensing, that this response is due to multiple complexation and subsequent aggregation of UFQDs. Nonetheless, the explanation of the distinct behaviour of transmittance in the presence of As(III) and the formation of precipitate with Pb2+require further studies. These differences, however, also make it possible to discriminate between the three metal ions in view of the implementation of a selective multiple sensor