Understanding neurological disease mechanisms in the era of epigenetics

Irfan A. Qureshi, Mark F. Mehler

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The burgeoning field of epigenetics is making a significant impact on our understanding of brain evolution, development, and function. In fact, it is now clear that epigenetic mechanisms promote seminal neurobiological processes, ranging from neural stem cell maintenance and differentiation to learning and memory. At the molecular level, epigenetic mechanisms regulate the structure and activity of the genome in response to intracellular and environmental cues, including the deployment of cell type-specific gene networks and those underlying synaptic plasticity. Pharmacological and genetic manipulation of epigenetic factors can, in turn, induce remarkable changes in neural cell identity and cognitive and behavioral phenotypes. Not surprisingly, it is also becoming apparent that epigenetics is intimately involved in neurological disease pathogenesis. Herein, we highlight emerging paradigms for linking epigenetic machinery and processes with neurological disease states, including how (1) mutations in genes encoding epigenetic factors cause disease, (2) genetic variation in genes encoding epigenetic factors modify disease risk, (3) abnormalities in epigenetic factor expression, localization, or function are involved in disease pathophysiology, (4) epigenetic mechanisms regulate disease-associated genomic loci, gene products, and cellular pathways, and (5) differential epigenetic profiles are present in patient-derived central and peripheral tissues.

Original languageEnglish (US)
Pages (from-to)703-710
Number of pages8
JournalJAMA Neurology
Volume70
Issue number6
DOIs
StatePublished - Jun 2013

Fingerprint

Epigenomics
Genetic Epigenesis
Neurological Disease
Epigenetics
Genes
Neuronal Plasticity
Neural Stem Cells
Gene Regulatory Networks
Cues
Cell Differentiation
Maintenance
Learning
Genome
Pharmacology
Phenotype
Mutation
Brain
Gene

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology

Cite this

Understanding neurological disease mechanisms in the era of epigenetics. / Qureshi, Irfan A.; Mehler, Mark F.

In: JAMA Neurology, Vol. 70, No. 6, 06.2013, p. 703-710.

Research output: Contribution to journalArticle

@article{66d93a954c334395be2a4f5ef2f98a0a,
title = "Understanding neurological disease mechanisms in the era of epigenetics",
abstract = "The burgeoning field of epigenetics is making a significant impact on our understanding of brain evolution, development, and function. In fact, it is now clear that epigenetic mechanisms promote seminal neurobiological processes, ranging from neural stem cell maintenance and differentiation to learning and memory. At the molecular level, epigenetic mechanisms regulate the structure and activity of the genome in response to intracellular and environmental cues, including the deployment of cell type-specific gene networks and those underlying synaptic plasticity. Pharmacological and genetic manipulation of epigenetic factors can, in turn, induce remarkable changes in neural cell identity and cognitive and behavioral phenotypes. Not surprisingly, it is also becoming apparent that epigenetics is intimately involved in neurological disease pathogenesis. Herein, we highlight emerging paradigms for linking epigenetic machinery and processes with neurological disease states, including how (1) mutations in genes encoding epigenetic factors cause disease, (2) genetic variation in genes encoding epigenetic factors modify disease risk, (3) abnormalities in epigenetic factor expression, localization, or function are involved in disease pathophysiology, (4) epigenetic mechanisms regulate disease-associated genomic loci, gene products, and cellular pathways, and (5) differential epigenetic profiles are present in patient-derived central and peripheral tissues.",
author = "Qureshi, {Irfan A.} and Mehler, {Mark F.}",
year = "2013",
month = "6",
doi = "10.1001/jamaneurol.2013.1443",
language = "English (US)",
volume = "70",
pages = "703--710",
journal = "JAMA Neurology",
issn = "2168-6149",
publisher = "American Medical Association",
number = "6",

}

TY - JOUR

T1 - Understanding neurological disease mechanisms in the era of epigenetics

AU - Qureshi, Irfan A.

AU - Mehler, Mark F.

PY - 2013/6

Y1 - 2013/6

N2 - The burgeoning field of epigenetics is making a significant impact on our understanding of brain evolution, development, and function. In fact, it is now clear that epigenetic mechanisms promote seminal neurobiological processes, ranging from neural stem cell maintenance and differentiation to learning and memory. At the molecular level, epigenetic mechanisms regulate the structure and activity of the genome in response to intracellular and environmental cues, including the deployment of cell type-specific gene networks and those underlying synaptic plasticity. Pharmacological and genetic manipulation of epigenetic factors can, in turn, induce remarkable changes in neural cell identity and cognitive and behavioral phenotypes. Not surprisingly, it is also becoming apparent that epigenetics is intimately involved in neurological disease pathogenesis. Herein, we highlight emerging paradigms for linking epigenetic machinery and processes with neurological disease states, including how (1) mutations in genes encoding epigenetic factors cause disease, (2) genetic variation in genes encoding epigenetic factors modify disease risk, (3) abnormalities in epigenetic factor expression, localization, or function are involved in disease pathophysiology, (4) epigenetic mechanisms regulate disease-associated genomic loci, gene products, and cellular pathways, and (5) differential epigenetic profiles are present in patient-derived central and peripheral tissues.

AB - The burgeoning field of epigenetics is making a significant impact on our understanding of brain evolution, development, and function. In fact, it is now clear that epigenetic mechanisms promote seminal neurobiological processes, ranging from neural stem cell maintenance and differentiation to learning and memory. At the molecular level, epigenetic mechanisms regulate the structure and activity of the genome in response to intracellular and environmental cues, including the deployment of cell type-specific gene networks and those underlying synaptic plasticity. Pharmacological and genetic manipulation of epigenetic factors can, in turn, induce remarkable changes in neural cell identity and cognitive and behavioral phenotypes. Not surprisingly, it is also becoming apparent that epigenetics is intimately involved in neurological disease pathogenesis. Herein, we highlight emerging paradigms for linking epigenetic machinery and processes with neurological disease states, including how (1) mutations in genes encoding epigenetic factors cause disease, (2) genetic variation in genes encoding epigenetic factors modify disease risk, (3) abnormalities in epigenetic factor expression, localization, or function are involved in disease pathophysiology, (4) epigenetic mechanisms regulate disease-associated genomic loci, gene products, and cellular pathways, and (5) differential epigenetic profiles are present in patient-derived central and peripheral tissues.

UR - http://www.scopus.com/inward/record.url?scp=84878805870&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878805870&partnerID=8YFLogxK

U2 - 10.1001/jamaneurol.2013.1443

DO - 10.1001/jamaneurol.2013.1443

M3 - Article

VL - 70

SP - 703

EP - 710

JO - JAMA Neurology

JF - JAMA Neurology

SN - 2168-6149

IS - 6

ER -