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Epigenetics, a key for unlocking complex CNS disorders? Therapeutic implications
Abstract
Aberrant changes in gene function are believed to be involved in a wide spectrum of human disease including behavioral, cognitive and neurodegenerative pathologies. Most of the attention in last few decades have focused on changes in gene sequence as a cause of gene dysfunction leading to disease and mental health disorders. Germ line mutations or other alterations in the sequence of DNA that associate with different behavioral and neurological pathologies have been identified. However, sequence alterations explain only a small fraction of the cases. In addition there is evidence for "gene-environment" interactions in the brain suggesting mechanisms that alter gene function and the phenotype through environmental exposure. Genes are programmed by "epigenetic" mechanisms such as chromatin structure, chromatin modification and DNA methylation. These mechanisms confer on similar sequences different identities during cellular differentiation. Epigenetic differences are proposed to be involved in differentiating gene function in response to different environmental contexts and could result in alterations in functional gene networks that lead to brain disease. Epigenetic markers could serve important biomarkers in brain and behavioral diseases. Moreover, epigenetic processes are potentially reversible pointing to epigenetic therapeutics in psychotherapy.
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“Yet, clinical application is still a long way off, and several caveats such as the lack of selectivity and specificity of currently available agents remain (see Szyf, 2015).”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Szyf, 2015
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“The response of the peripheral immune system to social adversity signals should not be surprising, as decades of studies have delineated bilateral relationship between the HPA axis and the immune system as well as between the immune system and brain function(Bellinger et al., 2008; Buske-Kirschbaum, 2009; Coe and Eric…”
BackgroundEarly demethylation of non-CpG, CpC-rich, elements in the myogenin 5’-flanking region
Fuso, A., Ferraguti, G., Grandoni, F., Ruggeri, R., Scarpa, S., Ström, R., & Lucarelli, M. (2010) · Cell Cycle · doi:10.4161/cc.9.19.13193 · Cited by 75
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Metadata
- Authors
- Szyf, M.
- Venue
- European Neuropsychopharmacology
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 25
- Issue
- 5
- Pages
- 682-702
- ISSN
- 0924-977X (ISSN-L)
- OpenAlex
- W1985697930
- Cited by
- 76
- References
- 248
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 7 · 2023: 14 · 2022: 2 · 2021: 2 · 2020: 7 · 2019: 8 · 2018: 2 · 2017: 8 · 2016: 9 · 2015: 7
- FWCI
- 0.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- epigenetics, central nervous system disorders, chromatin modification, DNA methylation, gene-environment interaction, epigenetic biomarkers, epigenetic therapy, neurodegenerative diseases, mental illness, chromatin structure, cell differentiation
- MeSH terms
- Animals, Central Nervous System Agents, Central Nervous System Diseases, Humans, Epigenesis, Genetic
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