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Epigenetic mechanisms in migraine: a promising avenue?

Eising E, A Datson N, van den Maagdenberg AM, Ferrari MD - BMC Med (2013)

Bottom Line: This review will focus on evidence that epigenetic mechanisms play an important role in disease etiology.Epigenetics comprise both DNA methylation and post-translational modifications of the tails of histone proteins, affecting chromatin structure and gene expression.Epigenetic mechanisms may explain how non-genetic endogenous and exogenous factors such as female sex hormones, stress hormones and inflammation trigger may modulate attack frequency.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Human Genetics, Leiden University Medical Centre, Einthovenweg 20, Leiden 2333 ZC, The Netherlands.

ABSTRACT
Migraine is a disabling common brain disorder typically characterized by attacks of severe headache and associated with autonomic and neurological symptoms. Its etiology is far from resolved. This review will focus on evidence that epigenetic mechanisms play an important role in disease etiology. Epigenetics comprise both DNA methylation and post-translational modifications of the tails of histone proteins, affecting chromatin structure and gene expression. Besides playing a role in establishing cellular and developmental stage-specific regulation of gene expression, epigenetic processes are also important for programming lasting cellular responses to environmental signals. Epigenetic mechanisms may explain how non-genetic endogenous and exogenous factors such as female sex hormones, stress hormones and inflammation trigger may modulate attack frequency. Developing drugs that specifically target epigenetic mechanisms may open up exciting new avenues for the prophylactic treatment of migraine.

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Proposed model in which epigenetic factors influence migraine pathophysiology. Different factors such as hormones, inflammation and neuronal activity can result in chromatin remodeling events affecting the expression of genes and pathways involved in the onset and progress of migraine and comorbid disorders such as depression. The hyperexcitability observed in migraine itself acts on the epigenome, thus creating a feed-forward loop resulting in chronification of migraine.
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Figure 1: Proposed model in which epigenetic factors influence migraine pathophysiology. Different factors such as hormones, inflammation and neuronal activity can result in chromatin remodeling events affecting the expression of genes and pathways involved in the onset and progress of migraine and comorbid disorders such as depression. The hyperexcitability observed in migraine itself acts on the epigenome, thus creating a feed-forward loop resulting in chronification of migraine.

Mentions: It is becoming increasingly clear that epigenetic processes play an important role in a wide variety of multifactorial diseases [3]. The question we aim to address here is: do they also play a role in migraine? Epigenetics encompasses changes to the DNA structure without changing the genetic code, resulting in chromatin remodeling and consequently affecting transcriptional potential and expression of genes. The main epigenetic modifications or 'marks' are post-translational modifications of the tails of histone proteins and DNA methylation, collectively comprising the epigenome (Figure 1). These marks are catalyzed by enzymes including histone deacetylases (HDACs), histone acetyltransferases (HATs) and DNA methyltransferases (DNMTs). Epigenetic marks can be dynamic but can also be stably inherited through cell divisions. Therefore, epigenetic processes enable cell and developmental stage-specific regulation of gene expression, but also play an important role in programming lasting responses to environmental cues.


Epigenetic mechanisms in migraine: a promising avenue?

Eising E, A Datson N, van den Maagdenberg AM, Ferrari MD - BMC Med (2013)

Proposed model in which epigenetic factors influence migraine pathophysiology. Different factors such as hormones, inflammation and neuronal activity can result in chromatin remodeling events affecting the expression of genes and pathways involved in the onset and progress of migraine and comorbid disorders such as depression. The hyperexcitability observed in migraine itself acts on the epigenome, thus creating a feed-forward loop resulting in chronification of migraine.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3584973&req=5

Figure 1: Proposed model in which epigenetic factors influence migraine pathophysiology. Different factors such as hormones, inflammation and neuronal activity can result in chromatin remodeling events affecting the expression of genes and pathways involved in the onset and progress of migraine and comorbid disorders such as depression. The hyperexcitability observed in migraine itself acts on the epigenome, thus creating a feed-forward loop resulting in chronification of migraine.
Mentions: It is becoming increasingly clear that epigenetic processes play an important role in a wide variety of multifactorial diseases [3]. The question we aim to address here is: do they also play a role in migraine? Epigenetics encompasses changes to the DNA structure without changing the genetic code, resulting in chromatin remodeling and consequently affecting transcriptional potential and expression of genes. The main epigenetic modifications or 'marks' are post-translational modifications of the tails of histone proteins and DNA methylation, collectively comprising the epigenome (Figure 1). These marks are catalyzed by enzymes including histone deacetylases (HDACs), histone acetyltransferases (HATs) and DNA methyltransferases (DNMTs). Epigenetic marks can be dynamic but can also be stably inherited through cell divisions. Therefore, epigenetic processes enable cell and developmental stage-specific regulation of gene expression, but also play an important role in programming lasting responses to environmental cues.

Bottom Line: This review will focus on evidence that epigenetic mechanisms play an important role in disease etiology.Epigenetics comprise both DNA methylation and post-translational modifications of the tails of histone proteins, affecting chromatin structure and gene expression.Epigenetic mechanisms may explain how non-genetic endogenous and exogenous factors such as female sex hormones, stress hormones and inflammation trigger may modulate attack frequency.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Human Genetics, Leiden University Medical Centre, Einthovenweg 20, Leiden 2333 ZC, The Netherlands.

ABSTRACT
Migraine is a disabling common brain disorder typically characterized by attacks of severe headache and associated with autonomic and neurological symptoms. Its etiology is far from resolved. This review will focus on evidence that epigenetic mechanisms play an important role in disease etiology. Epigenetics comprise both DNA methylation and post-translational modifications of the tails of histone proteins, affecting chromatin structure and gene expression. Besides playing a role in establishing cellular and developmental stage-specific regulation of gene expression, epigenetic processes are also important for programming lasting cellular responses to environmental signals. Epigenetic mechanisms may explain how non-genetic endogenous and exogenous factors such as female sex hormones, stress hormones and inflammation trigger may modulate attack frequency. Developing drugs that specifically target epigenetic mechanisms may open up exciting new avenues for the prophylactic treatment of migraine.

Show MeSH
Related in: MedlinePlus