TY - JOUR
T1 - Epigenetic mechanisms underlying human epileptic disorders and the process of epileptogenesis
AU - Qureshi, Irfan A.
AU - Mehler, Mark F.
N1 - Funding Information:
M.F.M. is supported by grants from the National Institutes of Health (NS38902, MH66290), as well as by the Roslyn and Leslie Goldstein, the Mildred and Bernard H. Kayden, the F. M. Kirby and the Alpern Family Foundations. We thank Dr. Solomon Moshe for critical reading of the manuscript.
PY - 2010/7
Y1 - 2010/7
N2 - The rapidly emerging science of epigenetics and epigenomic medicine promises to reveal novel insights into the susceptibility to and the onset and progression of epileptic disorders. Epigenetic regulatory mechanisms are now implicated in orchestrating aspects of neural development (e.g., cell fate specification and maturation), homeostasis and stress responses (e.g., immediate early gene transcription), and neural network function (e.g., excitation-inhibition coupling and activity-dependent plasticity). These same neurobiological processes are responsible for determining the heterogeneous features of complex epileptic disease states. Thus, we highlight recent evidence that is beginning to elucidate the specific roles played by epigenetic mechanisms, including DNA methylation, histone code modifications and chromatin remodeling, noncoding RNAs and RNA editing, in human epilepsy syndromes and in the process of epileptogenesis. The highly integrated layers of the epigenome are responsible for the cell type specific and exquisitely environmentally responsive deployment of genes and functional gene networks that underlie the molecular pathophysiology of epilepsy and its associated comorbidities, including but not limited to neurotransmitter receptors (e.g., GluR2, GLRA2, and GLRA3), growth factors (e.g., BDNF), extracellular matrix proteins (e.g., RELN), and diverse transcriptional regulators (e.g., CREB, c-fos, and c-jun). These important observations suggest that future epigenetic studies are necessary to better understand, classify, prevent, and treat epileptic disorders.
AB - The rapidly emerging science of epigenetics and epigenomic medicine promises to reveal novel insights into the susceptibility to and the onset and progression of epileptic disorders. Epigenetic regulatory mechanisms are now implicated in orchestrating aspects of neural development (e.g., cell fate specification and maturation), homeostasis and stress responses (e.g., immediate early gene transcription), and neural network function (e.g., excitation-inhibition coupling and activity-dependent plasticity). These same neurobiological processes are responsible for determining the heterogeneous features of complex epileptic disease states. Thus, we highlight recent evidence that is beginning to elucidate the specific roles played by epigenetic mechanisms, including DNA methylation, histone code modifications and chromatin remodeling, noncoding RNAs and RNA editing, in human epilepsy syndromes and in the process of epileptogenesis. The highly integrated layers of the epigenome are responsible for the cell type specific and exquisitely environmentally responsive deployment of genes and functional gene networks that underlie the molecular pathophysiology of epilepsy and its associated comorbidities, including but not limited to neurotransmitter receptors (e.g., GluR2, GLRA2, and GLRA3), growth factors (e.g., BDNF), extracellular matrix proteins (e.g., RELN), and diverse transcriptional regulators (e.g., CREB, c-fos, and c-jun). These important observations suggest that future epigenetic studies are necessary to better understand, classify, prevent, and treat epileptic disorders.
KW - Chromatin
KW - DNA methylation
KW - Epigenetic
KW - Epilepsy
KW - Histone
KW - Long noncoding RNA (lncRNA)
KW - MicroRNA (miRNA)
KW - Noncoding RNA (ncRNA)
KW - RNA editing
KW - Repressor element-1 silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF)
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U2 - 10.1016/j.nbd.2010.02.005
DO - 10.1016/j.nbd.2010.02.005
M3 - Review article
C2 - 20188170
AN - SCOPUS:77952887283
SN - 0969-9961
VL - 39
SP - 53
EP - 60
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 1
ER -