Epigenetic mechanisms in neurological and neurodegenerative diseases

Abstract

The role of epigenetic mechanisms in the function and homeostasis of the central nervous system (CNS) and its regulation in diseases is one of the most interesting processes of contemporary neuroscience. In the last decade, a growing body of literature suggests that long-term changes in gene transcription associated with CNS’s regulation and neurological disorders are mediated via modulation of chromatin structure. “Epigenetics”, introduced for the first time by Waddington in the early 1940s, has been traditionally referred to a variety of mechanisms that allow heritable changes in gene expression even in the absence of DNA mutation. However, new definitions acknowledge that many of these mechanisms used to perpetuate epigenetic traits in dividing cells are used by neurons to control a variety of functions dependent on gene expression. Indeed, in the recent years these mechanisms have shown their importance in the maintenance of a healthy CNS. Moreover, environmental inputs that have shown effects in CNS diseases, such as nutrition, that can modulate the concentration of a variety of metabolites such as acetyl-coenzyme A (acetyl-coA), nicotinamide adenine dinucleotide (NAD + ) and beta hydroxybutyrate (β-HB), regulates some of these epigenetic modifications, linking in a precise way environment with gene expression. This manuscript will portray what is currently understood about the role of epigenetic mechanisms in the function and homeostasis of the CNS and their participation in a variety of neurological disorders. We will discuss how the machinery that controls these modifications plays an important role in processes involved in neurological disorders such as neurogenesis and cell growth. Moreover, we will discuss how environmental inputs modulate these modifications producing metabolic and physiological alterations that could exert beneficial effects on neurological diseases. Finally, we will highlight possible future directions in the field of epigenetics and neurological disorders.

Pathogenic Mutations in the Valosin-containing Protein/p97(VCP) N-domain Inhibit the SUMOylation of VCP and Lead to Impaired Stress Response

“…Like epigenetic modifications (21), PTMs could be one of the links between environment input/life experiences and the functional regulation of disease-associated proteins in the decades leading to neurodegeneration. One form of PTMs is protein SUMOylation, which is a lysine modification homologous to ubiquitination, and is facilitated by the E1-activating enzymes SAE1 or SAE2, the solo E2 conjugating enzyme Ubc9 and various E3 ligases (22).…”

Introductory Chapter: Epigenetics in Summary

“…Therefore, genome activity is epigenetically modulated under exogenous influence, and the environment-dependent changes in gene activity stably propagate from one generation of cells to the next one. Epigenetic changes impact genome functions, thus affecting health and disease status and also behavior; aging-related diseases, cancer, immunity and related disorders, obesity, metabolic disorders, infertility, and cardiovascular and neurological diseases represent only few examples of environmentally dependent diseases, and the literature in the field is growing up day by day [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35].…”

Detection of Modified Forms of Cytosine Using Sensitive Immunohistochemistry

“…5mC is being introduced and maintained by DNA methyltransferases [2][3][4][5] , and has been shown to play important roles in a number of biological processes including genomic imprinting, X-chromosome inactivation, cellular differentiation, and development 3,6 . Consequently, the disruption of 5mC genomic patterns is associated with a number of diseases 7,[8][9][10][11] . Despite the progress in understanding 5mC role in development and disease, it is still remain largely unknown how this mark is being removed in developing and adult tissues.…”