Epigenetic mechanisms underlying nervous system diseases

Abstract

Epigenetic mechanisms act as control systems for modulating genomic structure and activity in response to evolving profiles of cell-extrinsic, cell-cell, and cell-intrinsic signals. These dynamic processes are responsible for mediating cell- and tissue-specific gene expression and function and gene-gene and gene-environmental interactions. The major epigenetic mechanisms include DNA methylation and hydroxymethylation; histone protein posttranslational modifications, nucleosome remodeling/repositioning, and higher-order chromatin reorganization; noncoding RNA regulation; and RNA editing. These mechanisms are intimately involved in executing fundamental genomic programs, including gene transcription, posttranscriptional RNA processing and transport, translation, X-chromosome inactivation, genomic imprinting, retrotransposon regulation, DNA replication, and DNA repair and the maintenance of genomic stability. For the nervous system, epigenetics offers a novel and robust framework for explaining how brain development and aging occur, neural cellular diversity is generated, synaptic and neural network connectivity and plasticity are mediated, and complex cognitive and behavioral phenotypes are inherited transgenerationally. Epigenetic factors and processes are, not surprisingly, implicated in nervous system disease pathophysiology through several emerging paradigms - mutations and genetic variation in genes encoding epigenetic factors; impairments in epigenetic factor expression, localization, and function; epigenetic mechanisms modulating disease-associated factors and pathways; and the presence of deregulated epigenetic profiles in central and peripheral tissues.

Genetics of migraine aura: an update

“…Another explanation for the missing heritability could be epigenetic processes. Epigenetics encompasses changes to the DNA structure without changing the genetic code and affects gene expression and has also been implicated in neurological disorders [30]. Epigenetic changes can be dynamic, be passed on through cell divisions or transgenerational inheritance.…”

Donald O. Hebb and the Organization of Behavior: 17 years in the writing

“…Semon's concept of the engram involved a number of 'Mnemonic Principles' applied to instincts, ontogeny, habit and 'inherited dispositions' and it was this latter principle of "transmission of acquired characteristics" which was "a heresy to most biologists" ( [141], page 337). Today we could interpret Semon's theory as the first attempt at an epigenetic theory of the effects of the environment on the brain and behaviour (see [30,156,158]). Semon's ideas influenced many areas of biology and psychology of which I mention three: evolutionary theory, psychoanalytic theory and the search for the locus of memory in the brain.…”

Epigenetic Analysis in Human Neurons: Considerations for Disease Modeling in PD

“…Epigenetic alterations of genes could contribute to the pathophysiology of this individual susceptibility (Landgrave-Gomez et al, 2015). Epigenetic modifications comprise DNA methylation, modification of histones, non-coding RNA regulation, RNA editing and nucleosome remodeling/positioning (Figure 1A) (Portela and Esteller, 2010; Wen et al, 2016; Qureshi and Mehler, 2018). These epigenetic modifications regulate gene expression without impact on the DNA sequence itself (Portela and Esteller, 2010; Wen et al, 2016; Qureshi and Mehler, 2018).…”

“…Epigenetic modifications comprise DNA methylation, modification of histones, non-coding RNA regulation, RNA editing and nucleosome remodeling/positioning (Figure 1A) (Portela and Esteller, 2010; Wen et al, 2016; Qureshi and Mehler, 2018). These epigenetic modifications regulate gene expression without impact on the DNA sequence itself (Portela and Esteller, 2010; Wen et al, 2016; Qureshi and Mehler, 2018). Epigenetic modifications regulate fundamental cellular processes (e.g., gene transcription, X-chromosome inactivation) and fill the gap between environmental and age-associated gene expression (Wen et al, 2016; Qureshi and Mehler, 2018).…”

“…These epigenetic modifications regulate gene expression without impact on the DNA sequence itself (Portela and Esteller, 2010; Wen et al, 2016; Qureshi and Mehler, 2018). Epigenetic modifications regulate fundamental cellular processes (e.g., gene transcription, X-chromosome inactivation) and fill the gap between environmental and age-associated gene expression (Wen et al, 2016; Qureshi and Mehler, 2018). They are dynamic, cell specific, display interindividual variability and can also occur in non-dividing cells such as neurons (Fraga et al, 2005; Feng et al, 2007; Fraga and Esteller, 2007).…”