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Epigenetic mechanisms in neurological and neurodegenerative diseases.

Landgrave-Gómez J, Mercado-Gómez O, Guevara-Guzmán R - Front Cell Neurosci (2015)

Bottom Line: 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.Indeed, in the recent years these mechanisms have shown their importance in the maintenance of a healthy CNS.Moreover, we will discuss how environmental inputs modulate these modifications producing metabolic and physiological alterations that could exert beneficial effects on neurological diseases.

View Article: PubMed Central - PubMed

Affiliation: Facultad de Medicina, Departamento de Fisiología, Universidad Nacional Autónoma de México México, D.F., México.

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.

No MeSH data available.


Related in: MedlinePlus

Histone posttranslational modifications. (A) Schemes representing the interaction of the N-terminal dominium of acetylated histones with the DNA strand (A) and the interaction of a non-acetylated histone with the DNA strand (B). It can be noticed that acetylated histones have a minor interaction with DNA strand compared with that of non-acetylated histones whose positive charges are attracted to negative charges of DNA. (C) On the other hand different specific marks of methylation of histone 3 are associated with both transcriptional activation (C) and repression (D). Also a specific mark of phosphorylation on the (S10) amino acid of histone 3 has been associated with transcriptional activation (E) so the lack of this mark may be associated with transcriptional repression (F).
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Figure 2: Histone posttranslational modifications. (A) Schemes representing the interaction of the N-terminal dominium of acetylated histones with the DNA strand (A) and the interaction of a non-acetylated histone with the DNA strand (B). It can be noticed that acetylated histones have a minor interaction with DNA strand compared with that of non-acetylated histones whose positive charges are attracted to negative charges of DNA. (C) On the other hand different specific marks of methylation of histone 3 are associated with both transcriptional activation (C) and repression (D). Also a specific mark of phosphorylation on the (S10) amino acid of histone 3 has been associated with transcriptional activation (E) so the lack of this mark may be associated with transcriptional repression (F).

Mentions: The principal residues that are substrates of these modifications are lysine, arginine, serine and threonine amino acids (Rothbart and Strahl, 2014). These modifications have been associated to repression or activation of gene transcription depending on the site of the modification, strongly suggesting the existence of a histone code. This hypothesis proposes that specific modifications of histones induce to the interaction with proteins associated with the chromatin, producing a differential regulatory response of gene expression (Strahl and Allis, 2000; Table 1 and Figure 2). These modifications are dynamic in the way that they are actively added and removed by histone-modifying enzymes in a site-specific manner, which is essential for coordinated transcriptional control.


Epigenetic mechanisms in neurological and neurodegenerative diseases.

Landgrave-Gómez J, Mercado-Gómez O, Guevara-Guzmán R - Front Cell Neurosci (2015)

Histone posttranslational modifications. (A) Schemes representing the interaction of the N-terminal dominium of acetylated histones with the DNA strand (A) and the interaction of a non-acetylated histone with the DNA strand (B). It can be noticed that acetylated histones have a minor interaction with DNA strand compared with that of non-acetylated histones whose positive charges are attracted to negative charges of DNA. (C) On the other hand different specific marks of methylation of histone 3 are associated with both transcriptional activation (C) and repression (D). Also a specific mark of phosphorylation on the (S10) amino acid of histone 3 has been associated with transcriptional activation (E) so the lack of this mark may be associated with transcriptional repression (F).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4343006&req=5

Figure 2: Histone posttranslational modifications. (A) Schemes representing the interaction of the N-terminal dominium of acetylated histones with the DNA strand (A) and the interaction of a non-acetylated histone with the DNA strand (B). It can be noticed that acetylated histones have a minor interaction with DNA strand compared with that of non-acetylated histones whose positive charges are attracted to negative charges of DNA. (C) On the other hand different specific marks of methylation of histone 3 are associated with both transcriptional activation (C) and repression (D). Also a specific mark of phosphorylation on the (S10) amino acid of histone 3 has been associated with transcriptional activation (E) so the lack of this mark may be associated with transcriptional repression (F).
Mentions: The principal residues that are substrates of these modifications are lysine, arginine, serine and threonine amino acids (Rothbart and Strahl, 2014). These modifications have been associated to repression or activation of gene transcription depending on the site of the modification, strongly suggesting the existence of a histone code. This hypothesis proposes that specific modifications of histones induce to the interaction with proteins associated with the chromatin, producing a differential regulatory response of gene expression (Strahl and Allis, 2000; Table 1 and Figure 2). These modifications are dynamic in the way that they are actively added and removed by histone-modifying enzymes in a site-specific manner, which is essential for coordinated transcriptional control.

Bottom Line: 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.Indeed, in the recent years these mechanisms have shown their importance in the maintenance of a healthy CNS.Moreover, we will discuss how environmental inputs modulate these modifications producing metabolic and physiological alterations that could exert beneficial effects on neurological diseases.

View Article: PubMed Central - PubMed

Affiliation: Facultad de Medicina, Departamento de Fisiología, Universidad Nacional Autónoma de México México, D.F., México.

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.

No MeSH data available.


Related in: MedlinePlus