There are currently no validated biomarkers which can be used to accurately diagnose Alzheimer’s disease (AD) or to distinguish it from other dementia-causing neuropathologies. Moreover, to date, only symptomatic treatments exist for this progressive neurodegenerative disorder. In the search for new, more reliable biomarkers and potential therapeutic options, epigenetic modifications have emerged as important players in the pathogenesis of AD. The aim of the article was to provide a brief overview of the current knowledge regarding the role of epigenetics (including mitoepigenetics) in AD, and the possibility of applying these advances for future AD therapy. Extensive research has suggested an important role of DNA methylation and hydroxymethylation, histone posttranslational modifications, and non-coding RNA regulation (with the emphasis on microRNAs) in the course and development of AD. Recent studies also indicated mitochondrial DNA (mtDNA) as an interesting biomarker of AD, since dysfunctions in the mitochondria and lower mtDNA copy number have been associated with AD pathophysiology. The current evidence suggests that epigenetic changes can be successfully detected, not only in the central nervous system, but also in the cerebrospinal fluid and on the periphery, contributing further to their potential as both biomarkers and therapeutic targets in AD.

Background: Given that approximately 70% of miRNAs in the body are neuronal, we critically assessed current studies on miRNAs and suicidal behavior. Materials & Methods: To further define the role ...

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder affecting women of reproductive age. Research has shown that epigenetic alterations such as DNA methylation may play a role in the development and progression of abnormal ovarian function and metabolic disorders in PCOS. Studies have identified specific genes (related with insulin signaling and steroid hormone metabolism) that are methylated in women with PCOS. DNA methylation appears to respond to various interventions aimed at altering health and lifestyle factors. We tested the efficacy of a mindfulness-based stress reduction program (MBSR) in PCOS patients. We examined its effects on anthropometric measurements, mental health and wellbeing, and alterations in DNA methylation in peripheral blood. MBSR was associated with a reduction in body mass index, waist circumference and blood glucose level, an improvement in subjectively perceived general health, emotional role limitation, and levels of pain, as well as mindfulness-like traits. MBSR reduced the expression of anxious symptomatology and subjectively perceived stress. Methylation changes were observed in four genes: COMT, FST, FKBP51, and MAOA. We conclude that MBSR may be a useful supplementary therapy to mitigate the deleterious effects of PCOS on mental health.

Suicide is an important public‐health concern, with more than 700,000 people dying by suicide yearly. It is a multifactorial phenomenon, shaped by the effects of sociodemographic, environmental and biological factors. The latter two factors can be linked through epigenetic studies, which examine differences in gene expression that are not due to changes in the DNA sequence itself. Epigenetic mechanisms include micro RNAs (miRNAs), which have a direct effect on already translated mRNA, leading to either decay or translational repression of the target mRNA. MiRNA molecules have been identified as cargo of extracellular vesicles (EVs) used by cells for long‐distance communication, and pathophysiological changes in miRNA in brain cells may be reflected in cerebrospinal fluid (CSF) vesicles. In this study we investigated the presence and differential expression of selected miRNAs in EVs from the CSF of male suicide completers and controls. Western blot and nanoparticle tracking analyses confirmed the presence of small and medium sized EVs. Of the miRNA analyzed (miR‐16‐5p, miR‐19a‐3p, miR‐34c‐5p, miR‐17‐5p, miR‐4286, miR‐26b‐5p, miR‐381‐3p, and miR‐4516) miR‐19a‐3p and miR‐4516 reached statistical significance with p‐values of 0.0408 and 0.0168, respectively. Mir‐4516 and miRNA‐19a‐3p have been previously studied in suicide, and target SLC6A4 and TNF‐α expression, correspondingly. Approximately 70% of known miRNAs are expressed in the central nervous system, and therefore represent an important biomarker potential. Investigating the cargo of CFS and blood EVs would further support the identification of miRNAs with clinical use potential.

Due to the increasing number of progressive dementias in the population, numerous studies are being conducted that seek to determine risk factors, biomarkers and pathological mechanisms that could help to differentiate between normal symptoms of aging, mild cognitive impairment (MCI) and dementia. The aim of this study was to investigate the possible association of levels of BDNF and COMT gene expression and methylation in peripheral blood cells with the development of Alzheimer’s disease (AD). Our results revealed higher expression levels of BDNF (p < 0.001) in MCI subjects compared to individuals diagnosed with AD. However, no difference in COMT gene expression (p = 0.366) was detected. DNA methylation of the CpG islands and other sequences with potential effects on gene expression regulation revealed just one region (BDNF_9) in the BDNF gene (p = 0.078) with marginally lower levels of methylation in the AD compared to MCI subjects. Here, we show that the level of BDNF expression in the periphery is decreased in subjects with AD compared to individuals with MCI. The combined results from the gene expression analysis and DNA methylation analysis point to the potential of BDNF as a marker that could help distinguish between MCI and AD patients.

Glioblastoma is simultaneously the most common and most aggressive primary brain tumor in the central nervous system, with poor patient survival and scarce treatment options. Most primary glioblastomas reoccur and evolve radio- and chemoresistant properties which make them resistant to further treatments. Based on gene mutations and expression profiles, glioblastoma is relatively well classified; however, research shows that there is more to glioblastoma biology than that defined solely by its genetic component. Specifically, the overall malignancy of the tumor is also influenced by the dynamic communication to its immediate and distant environment, as important messengers to neighboring cells in the tumor microenvironment extracellular vesicles (EVs) have been identified. EVs and their cargo can modulate the immune microenvironment and other physiological processes, and can interact with the host immune system. They are involved in tumor cell survival and metabolism, tumor initiation, progression, and therapy resistance. However, on the other hand EVs are thought to become an effective treatment alternative, since they can cross the blood–brain barrier, are able of specific cell-targeting and can be loaded with various therapeutic molecules.